Energy hubs by interconnecting various energy systems give rise to the multi carrier energy (MCE) system, as the upcoming energy providing system. The appropriate design and operation of microgrids (MGs) are essential in the MCE systems. In this paper, the self-adequacy improvement of MG within an MCE system is got under studied while achieving an optimal design for MGs. It is considered that the constructed MGs operate in both grid-connected and islanded modes. In other words, separating the designed zones leads to independent performance of the MGs which give more importance to the supply-adequacy context. Implementing the mentioned problem to real systems leads to a large scale, nonlinear problem which should be optimized using the robust optimization techniques. A modified version of group search optimization (GSO) algorithm is utilized in order to solve such problem. In order to obtain reasonable results and perform analytical evaluations, some efficient indices are proposed. Afterwards, the proposed scheme is applied to an 11-hubs test system and the obtained results are analyzed and discussed.

Biofilms can increase pathogenic contamination of drinking water, cause biofilm-related diseases, alter the sediment erosion rate, and degrade contaminants in wastewater. Compared with mature biofilms, biofilms in the early-stage have been shown to be more susceptible to antimicrobials and easier to remove. Mechanistic understanding of physical factors controlling early-stage biofilm growth is critical to predict and control biofilm development, yet such understanding is currently incomplete. Here, we reveal the impacts of hydrodynamic conditions and microscale surface roughness on the development of early-stage Pseudomonas putida biofilm through a combination of microfluidic experiments, numerical simulations, and fluid mechanics theories. We demonstrate that early-stage biofilm growth is suppressed under high flow conditions and that the critical local velocity for early-stage P. putida biofilms to develop is about 50 μm/s, similar to P. putida’s swimming speed. We further illustrate that microscale surface roughness promotes the growth of early-stage biofilms by increasing the area of the low-flow region. Furthermore, we show that the critical average shear stress, above which early-stage biofilms cease to form, is 0.9 Pa for rough surfaces, three times as large as the value for flat or smooth surfaces (0.3 Pa). The important control of flow conditions and microscale surface roughness on early-stage biofilm development, characterized in this study, will facilitate future predictions and managements of early-stage P. putida biofilm development on the surfaces of drinking water pipelines, blood vessels, and sediments in aquatic environments.

The objective of this research was to investigate the effect of temperature on the glycerolysis-interesterification reaction kinetics of immiscible and high viscous reactants at relatively low temperatures in a high shear reactor (HSR), and their physical product properties. The reaction was performed at various temperatures (80-120°C) and a mixing rate of 2000 rpm for 5 h. Results showed that the reaction rate constant increased and followed the Arrhenius equation as temperature increased. TAG conversion was 2.5 fold greater at 110 and 120°C compared to lower reaction temperatures. MAG and DAG increased by about 18.3% and 13.4%, respectively, as the reaction temperature increased from 80 to 120°C. The product’s melting point, hardness, and color were also improved by increasing temperature. In summary, structured lipids (SLs) synthesis containing high MAG and DAG could be produced at a relatively low temperature (110°C) using HSR, and followed the glycerolysis-interesterification kinetic and Arrhenius model.

Actin is an abundant and multifaceted protein in eukaryotic cells that has been detected in the cytoplasm as well as in the nucleus. In cooperation with numerous interacting accessory-proteins, monomeric actin (G-actin) polymerizes into microfilaments (F-actin) which constitute ubiquitous subcellular higher order structures. Considering the extensive spatial dimensions and multifunctionality of actin super-arrays, the present study analyses the issue if and to what extent environmental stress factors, specifically ionizing radiation (IR) and reactive oxygen species (ROS), affect the cellular actin-entity. In that context, this review particularly surveys IR-response of fungi and plants. It examines in detail which actin-related cellular constituents and molecular pathways are influenced by ionizing radiation and related ROS. This comprehensive survey concludes that the general integrity of the total cellular actin cytoskeleton is a requirement for IR-tolerance. Actin´s functions in genome organization and nuclear events like chromatin remodelling, DNA-repair, and transcription play a key role. Beyond that, it is highly significant that the macromolecular cytoplasmic and cortical actin-frameworks are affected by IR as well. In response to IR, actin-filament bundling proteins (fimbrins) are required to stabilize cables or patches. In addition, the actin-associated factors mediating cellular polarity are essential for IR-survivability. Moreover, it is concluded that a cellular homeostasis system comprising ROS, ROS-scavengers, NADPH-oxidases, and the actin cytoskeleton plays an essential role here. Consequently, besides the actin-fraction which controls crucial genome-integrity, also the portion which facilitates orderly cellular transport and polarized growth has to be maintained in order to survive IR.

Few textbooks on research methods offer more than a few words of advice on how to devise scientific hypotheses. Big data is conceived as a hypothesis-generator procedure, a disruptive analytical innovation that is reconfiguring ecological research. My theses are (a) the hypotheses that big-data can originate “stricto sensu” are empirical generalizations that do not provide ecological understanding, (b) empirical generalizations may encourage instrumentalist research, but cannot supply ecological explanation, and (c) generalizations emerging from data-driven research can serve as a problem-generating procedure if they are reflected in the context of the theoretical framework surrounding the research. Discovery (e.g., novel patterns shown by big-data analysis) and invention (e.g., hypotheses on mechanisms and processes conjectured by the human mind) are complementary tools in ecological research because they play different epistemological roles. Data-driven research provides a useful analytical tool, but it does not justify any epistemological or methodological paradigm shift.

Objective To report our recent experience managing ultra-high-risk gestational trophoblastic neoplasia (GTN) patients with liver and brain metastases. Design A retrospective review of data from a national gestational trophoblastic disease centre. Setting The Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China. Sample Total of 298 GTN patients recruited from January 2014 to December 2017. Main outcome measures The CR rate and drug-resistance rate after initial treatment of ultra-high-risk GTN patients with liver or brain metastases. Methods The clinical characteristics and treatment and prognosis outcomes in 11 ultra-high-risk GTN patients with liver or brain metastases were performed by descriptive analyses. The prognostic factors for death in all GTN patients were identified by Cox proportional hazards regression. Survival analysis were used to analyze survival time between GTN patients stratified according to liver or brain metastases. Results. The CR rate and drug-resistance rate after initial treatment of ultra-high-risk GTN patients with liver or brain metastases was 0% and 90.9% respectively, but the 5-year OS rate was 81.8% (n=11). Liver metastases (hazard ratio [HR]: 34.05; 95% confidence interval [CI]: 1.65–703.7; P=0.02) and brain metastases (HR: 49.19; 95% CI: 5.6–432.1; P<0.01) were independently significant risk factors for death in all GTN patients. Conclusions. Liver and brain metastases were found to be independently significant risk factors for death in all GTN patients. The drug-resistance rate with initial treatment was 90.9% in ultra-high-risk GTN patients with liver or brain metastases.

Background: RIF is a frustrating condition, both for the clinician and the patient. Clinical trials have shown that PRP might improve live birth and clinical pregnancy rate in women with RIF undergoing IVF. Materials, setting, and methods: An electronic database search of PubMed, EMBASE, SCOPUS, and Cochrane Central was performed for articles published in the English language by two independent reviewers using predefined eligibility criteria Women of reproductive age group diagnosed with RIF and are planned for IVF cycle with fresh or frozen embryos were included. Included studies were clinical trials comparing PRPa against routine care or used as a standalone therapy in patients with RIF. Bias was assessed using the Cochrane Collaboration Network Risk of Bias Tool version 2. Quality of evidence was determined and a summary of findings table was prepared for individual outcomes using GRADEpro software. Main results and the role of chance: We identified 1146 records, of which, we screened 531 records and ten studies were included for final review. For live birth rate, we have little confidence that administration of PRP had any significant effect on live birth rate (RR 3.01, 95% CI 1.13 to 7.99, I2 = 80%, very low quality of evidence). Similarly, the quality of evidence was low for clinical pregnancy rate, we are uncertain that the administration of PRP had any significant effect on clinical pregnancy rate (RR 2.09, 95% CI 1.71 to 2.55, I2 = 25%). The protocol was registered on PROSPERO (registration number CRD42021292209).

Background: Multiple gestation has a higher incidence of preterm birth(PTB), especially in the presence of a short cervix. Objectives: To perform a systematic review and network meta-analysis(NMA) evaluating the effect of progesterone, cerclage, cervical pessary and their combination as treatments for preventing PTB<34 weeks. Search strategy: PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science, BVS, Scopus, and grey literature were explored. Selection criteria: We included randomized controlled trials that compared an intervention with a control group or another intervention to prevent PTB in women with a twin pregnancy and a short cervix<40mm. Data collection and Analysis:Studies were checked for trustworthiness. We presented summary relative effect sizes(Odds Ratios) for each possible pair of interventions and we used the surface under the cumulative ranking curves(SUCRA) to rank all interventions. Main Results: A total of 20 studies participated in NMA. We found no evidence that the combined treatment of pessary and vaginal progesterone reduced the risk of spontaneous PTB <34 weeks when compared to no intervention(OR 0.68; 95%CI 0.16 to 2.9). Also, pessary(OR 0.78; 95%CI 0.49 to 1.3), vaginal progesterone(OR 0.79; CI95% 0.45 to 1.4) and injectable 17-OH progesterone alone(OR 0.85; CI95% 0.26 to 2.8) did not show a statistically significant reduction in spontaneous PTB. For overall PTB<34 weeks, findings were similar. Conclusions: We found no evidence that progesterone, cervical pessary, cerclage or their combination reduce PTB<34 weeks. There is an urgent need for randomized trials assessing these treatments in women with a multiple pregnancy and a short cervix.

Cuproptosis, the current form of regulated cell death characterized by copper overload, oligomerization of lipoacylated proteins, and loss of the Fe-S cluster proteins, has been proposed to function closely with human diseases including cancer. Since the first identification in 2022, a wide range of strategies have been developed to induce cuproptosis for cancer therapy, such as small-molecule drugs and nanomaterials. Although many reviews related to cuproptosis have been reported, they remain at a basic mechanism level and a summary covering recent progress in the field of nanotechnologies in cuproptosis-based cancer therapy has not yet been presented. Therefore, it is time to fill the gap and shed light on future directions for the application of this promising tool to fight against cancer. In this minireview, we first expounded the mechanism of action of cuproptosis and emphasized the feasibility of triggering cuproptosis for cancer therapy. The recent progress of cancer treatments based on nanoparticle-induced cuproptosis was then described. Finally, the challenges and future development directions of the emerging field of cuproptosis were also discussed.

BJOG-22-0767.R1 Multimorbidity warrants a proactive management of pregnancy in cancer survivors

Background and Purpose: Pleural mesothelioma (PM) is a highly aggressive thoracic tumor with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. Experimental Approach: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and correlated with clinicopathological features. Key Results: In surgically resected PM specimens, mean Pt levels were significantly higher in the non-tumorous (fibrotic) areas (vs. tumorous regions, p<0.001). No major heterogeneity of Pt distribution was seen within the tumorous areas. Pt levels correlated neither with microvessel area (MVA) nor with apoptosis rate in the tumorous or in the non-tumorous regions. A significant positive correlation was found between serum and both full tissue section and tumorous area average Pt levels (r=0.415, p=0.039 and r=0.532, p=0.006, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r=-0.474, p=0.017). Serum Pt levels correlated negatively with overall survival (OS) (p=0.029). Conclusion and Implications: There are major differences in the drug distribution between tumorous and non-tumorous areas of PM specimens. Serum Pt levels significantly correlate with full section- and tumorous areas average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.

Brugada patterns are masked and usually are due to provocative factors. We present a case of a 23-year-old Caucasian male patient with a long-standing history of substance abuse who presented with a syncope. EKG performed by EMS showed Brugada EKG pattern.

Cas13 are the only CRISPR/Cas systems found so far, which target RNA strand while preserving chromosomal integrity. Cas13b or Cas13d cleaves RNA by the crRNA guidance. However, the effect of the characteristics of the spacer sequences, such as the length and sequence preference, on the activity of Cas13b and Cas13d remains unclear. Our study shows that neither Cas13b nor Cas13d has a particular preference for the sequence composition of gRNA, including the sequence of crRNA and its flanking sites on target RNA. However, the crRNA, complementary to the middle part of the target RNA, seems to show higher cleavage efficiency for both Cas13b and Cas13d. As for the length of crRNAs, the most appropriate crRNA length for Cas13b is 22-25 nt and crRNA as short as 15 nt is still functional. Whereas, Cas13d requires longer crRNA, and 22-30 nt crRNA can achieve good effect. Both Cas13b and Cas13d show the ability to process precursor crRNAs. Our study suggests that Cas13b may have a stronger precursor processing ability than Cas13d. There are few in vivo studies on the application of Cas13b or Cas13d in mammals. With the methods of transgenic mice and hydrodynamic injection via tail vein, our study showed that both of them had high knock-down efficiency against target RNA in vivo. These results indicate that Cas13b and Cas13d have great potential for in vivo RNA operation and disease treatment without damaging genomic DNA.

Urbanization-induced environmental changes such as habitat fragmentation impacts arthropod assemblages and food web-related ecosystem functions, such as nutrient cycling, carbon storage and energy fluxes. Yet, we lack insight into how arthropod food webs are structured along urban fragmentation gradients. Here, we investigated the community composition and food web structure of litter-dwelling arthropods along fragmentation gradients (green median strip, urban park, urban forest and natural forest). We found the density of litter-dwelling arthropods in median strip and urban park to be two to four times higher than in urban and natural forests, with, as indicated by literature-based stable isotope values, 67% - 68% of the individuals comprising primary consumers (trophic level I) in median strip and urban park. Urban forests, reserved for biodiversity conservation, hosted the least arthropod density, taxa richness, biomass and body mass, but were colonized by a high number of specialist arthropods, e.g. Archaeognatha and Isoptera. Food webs were most simple in urban forest, but more complex in median strip and urban parks, i.e. open fragments, with abundant primary and secondary consumers including decomposers. Chilopoda and Araneae formed the apex predators in fragments and mostly consumed other predators of trophic level III. The biomass of decomposed litter on the soil surface as major resource of the soil animal community significantly correlated positively with the density of arthropods of trophic levels I, III and IV. Supporting the dominance of bottom-up forces, the density of adjacent trophic levels consistently correlated positively. Overall, our results suggest that small size urban fragments maintain a diverse community of arthropods forming complex food webs and thereby may contribute to conserving biodiversity and providing important ecosystem functions.

Fish community biomass is generally thought to decline with increasing temperature due to higher metabolic losses resulting in less efficient energy transfer in warm-water food webs. However, whether these metabolic predictions explain observed macroecological patterns in fish community biomass is virtually unknown. Here we test these predictions by examining the variation in demersal fish biomass across 21 productive shelf regions using high-resolution monitoring data from the North Atlantic and Northeast Pacific. We find that biomass per km2 varies 40-fold across regions and is highest in cold waters and areas with low fishing exploitation. We find no evidence that temperature change has impacted biomass within marine regions over time. Yet, the cross-regional patterns suggest that long-term impacts of warming will be negative on biomass. These results provide an empirical basis for predicting future changes in fish community biomass and its associated services for human wellbeing i.e., food provisioning, under global warming.

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest known adhesion G protein-coupled receptor. Mutations in VLGR1/ADGRV1 cause Usher syndrome (USH), the most common form of hereditary deaf-blindness, and have been additionally linked to epilepsy. Although VLGR1/ADGRV1 is almost ubiquitously expressed, little is known about the subcellular function and signalling of the VLGR1 protein and thus about mechanisms underlying the development of diseases. Using affinity proteomics, we have identified key components of autophagosomes as putative interacting proteins of VLGR1. In addition, whole transcriptome sequencing of the retinae of the Vlgr1/del7TM mouse model revealed altered expression profiles of gene-related autophagy. Monitoring autophagy by immunoblotting and immunocytochemistry of the LC3 and p62 as autophagy marker proteins revealed evoked autophagy in VLGR1-deficient hTERT-RPE1 cells and USH2C patient-derived fibroblasts. Our data demonstrate the molecular and functional interaction of VLGR1 with key components of the autophagy process and point to an essential role of VLGR1 in the regulation of autophagy at internal membranes. The close association of VLGR1 with autophagy helps to explain the pathomechanisms underlying human USH and epilepsy-related to VLGR1 defects.

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor aGPCRs. Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome (USH), the most common form of deaf-blindness, and also with epilepsy in humans and in mice. Although VLGR1 is almost ubiquitously expressed in CNS and ocular and inner ear sensory cells. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FA) serving as a metabotropic mechanoreceptor that controls cell spreading and migration. FAs are highly dynamic and turnover frequently in response to internal and external signals. Here, we aimed to elucidate how VLGR1 participates in FA turnover. Nocodazole washout assays and live-cell imaging of RFP-paxillin consistently demonstrated that FA disassembly was not altered, de novo assembly of FA was significantly delayed in Vlgr1-deficient astrocytes indicating that VLGR1 is enrolled in the assembly of FAs. In FRAP experiments recovery rates were significantly reduced in Vlgr1-deficient FAs, indicating reduced turnover kinetics in VLGR1-deficient FAs. We showed that VLGR1 regulates cell migration by controlling the FA turnover during their assembly. From this, we expect novel insights into pathomechanisms related to pathogenic dysfunctions of VLGR1.

High-throughput measurements of photosynthesis of plants grown under various conditions may provide important insights into the plasticity of the photosynthetic performance of plants. Remote sensing of photosynthetic activity [i.e., solar-induced chlorophyll fluorescence (SIF)] and its derivatives are the next generation of remote techniques, enabling high-throughput photosynthesis measurements under field conditions. We hypothesized that by measuring SIF simultaneously with measurements of whole-plant water relations in a standardized controlled drought experiment, we would be able to quantify photosynthetic activity and to detect water stress at an early stage. A functional-phenotyping platform was used to apply the controlled drought treatment and to monitor the growth and water balance of tomato introgression lines (ILs). A new SIF-derived index, electron transport rate (RS-ETRi), was found to be negatively correlated with whole-plant stomatal conductance (Gsc) under non-stressed conditions; whereas a positive correlation was observed between those factors under drought stress. No significant relationships were found between SIF and plant biomass or Gsc. SIF 687 responded to drought earlier than any of the other measured vegetation indices (VIs). SIF parameters could not differentiate between IL lines; whereas differences between ILs were clearly identified by the gravimetric water-relations measurements. We concluded that SIF did not provide any advantage over commonly used methods for detecting physiological differences between the ILs. Overall, although SIF plays a significant role in photosynthesis, the relationship between SIF and photosynthesis is complex and we believe it would be an oversimplification to use SIF to quantify photosynthetic activity.

Bone lesions are rarely reported in Hairy Cell Leukemia (HCL). We report two BRAFV600E mutated HCL patients presented bone lesions at foreground, poor bone marrow involvement and the important role 18F-FDG PET/CT played in their management. We discuss the crucial role that 18F-FDG PET/CT could play in HCL routine practice.

Cutaneous leiomyomas are benign tumors arising from smooth muscles of the skin. Multiple lesions may be arranged in segmental, zosteriform, disseminated patterns. Multiple pilar leiomyomas may be inherited in an autosomal dominant pattern and may be associated with uterine fibroids and renal cell carcinoma, also known as Reed Syndrome.

Phytochemicals are greatly ignored in trait-based ecology. Especially, the adaptations of phytochemicals to abiotic and biotic pressures in the rhizosphere are less understood. Here, we measured the metabolomics of fine roots and their rhizosphere microbiome along a climatic gradient (tropical, subtropical, and subalpine forests), to explore phytochemical diversity patterns and phytochemical-microorganism interactions. We found that high phytochemical diversity but low phytochemical endemism in subalpine species favor coping with high abiotic pressures. High phytochemical variation and phytochemical endemism in tropical species favor greater species coexistence and adaptation to complex biotic pressures. Moreover, there was evidence of widespread chemical niche partitioning of closely related species in all regions. Our findings support the Latitudinal Biotic Interaction Hypothesis, i.e., the intensity of phytochemical-microorganism interactions decreases from tropical to subalpine regions, which promotes greater multi-trophic coexistence in the tropics than in higher latitude forests. Our study provides novel insights into biotic interactions and species coexistence.

Transaction throughput is an important indicator of blockchain performance. However, many current smart contract virtual machines have low efficiency in executing smart contract transactions, which results in low transaction throughput of the blockchain. Some transaction parallel execution approaches have effectively improved transaction execution efficiency, but there are still problems such as low parallelism and large-scale transaction rollbacks. Therefore, we propose FSC, a fast execution approach for smart contract transactions based on fine-grained read-write analysis. The key idea is to obtain fine-grained read-write information from the smart contract compiler, and use this read-write information to group transactions at the blockchain platform layer, thereby improving the parallelism of transaction execution. FSC mainly includes three parts of work: 1) a fine-grained analysis method for read-write information at the contract state variable level based on the contract compiler; 2) a series of merging rules for merging read-write items; 3) a method to handle conflicting transactions. Our evaluation results show that FSC can accelerate the execution of smart contract transactions. Compared with before, FSC can reduce the overall transaction execution latency by 58.1%. In addition, FSC can shorten the longest execution path by 89.9% when the variation in transaction grouping latency is within 5.5%.

JSON is a popular standard for data interchange on the Internet. Ingesting JSON documents can be a performance bottleneck. A popular parsing strategy consists in converting the input text into a tree-based data structure—sometimes called a Document Object Model or DOM. We designed and implemented a novel JSON parsing interface—called On-Demand—that appears to the programmer like a conventional DOM-based approach. However, the underlying implementation is a pointer iterating through the content, only materializing the results (objects, arrays, strings, numbers) lazily. On recent commodity processors, an implementation of our approach provides superior performance in multiple benchmarks. To ensure reproducibility, our work is freely available as open source software.

Recently, Kubernetes is widely used to manage and schedule the resources of microservices in cloud-native distributed applications, as the most famous container orchestration framework. However, Kubernetes preferentially schedules microservices to nodes with rich and balanced CPU and memory resources on a single node. The native scheduler of Kubernetes, called Kube-scheduler, may cause resource fragmentation and decrease resource utilization. In this paper, we propose a deep reinforcement learning enhanced Kubernetes scheduler named DRS. To improve resource utilization and reduce load imbalance, we first present the Kubernetes scheduling problem as a Markov decision process and elaborately designed the state, action, and reward. Then, we design and implement DRS mointor to perceive six metrics about resource utilization to construct a comprehensive global resource view. Finally, DRS can automatically learn the scheduling policy through interaction with the Kubernetes cluster, without relying on expert knowledge about workload and cluster status. We implement a prototype of DRS in a Kubernetes cluster with five nodes and evaluate its performance. Experimental results highlight that DRS overcomes the shortcomings of Kube-scheduler and achieve the expected scheduling target with three workloads. Compared with Kube-scheduler, DRS brings an improvement of 27.29% in resource utilization and reduce the load imbalance by 2 .90× on average, with only 3.27% CPU overhead and 0.648% communication latency.