We investigated the impact of the human-specific protein CHRFAM7A (also referred to as “dupα7”) on the function of α7 nicotinic acetylcholine receptors (nAChRs) in two different types of neurons: human induced pluripotent stem cell (hiPSC)-derived cortical neurons, and superior cervical ganglion (SCG) neurons, taken from transgenic mice expressing CHRFAM7A. CHRFAM7A co-assembles with α7 (also referred to as CHRNA7) but lacks a major part of the extracellular N-terminal ligand-binding domain. We assessed the function of α7 in these preparations with Fura-2 calcium imaging and three different α7-specific ligands: PNU282987, choline, and 4BP-TQS. Given the short-lived open state of α7 receptors, we combined the two orthosteric agonists with the type-2 positive allosteric modulator (PAM II) PNU120596. In line with different cellular models used previously we demonstrate in primary human iPS-derived and in mouse neurons that CHRFAM7A has a major impact on nicotinic α7 receptors by reducing calcium transients in response to all three agonists.

This paper proposes a novel coreless multiphase magnetic resonant motor (MMRM) with a high torque per unit volume density (77.6 Nm/m 3) based on the properties of magnetic resonance coupling. In the proposed model, the conventional magnetic circuit in electric motors is replaced with that of a resonant circuit. Resonant capacitors are connected across the separate multiphase windings to produce the required resonance behavior in the machine. Analytical models of the machine's characteristics, such as inductance, generated torque, and capacitance estimation are derived and verified with an equivalent simulation model through finite element methods. The key is to efficiently integrate electric machine design concepts with inductive magnetic resonance coupling technology to enhance the output torque in an air-cored machine. The motor consists of a two-phase multiphase stator and rotor windings arranged radially on non-magnetic cores made from reinforced plastic fiber. Finally, a prototype is manufactured, and the effectiveness of the MMRM is validated by experimental results. To evaluate the significance of the proposed design, a case-control experiment without resonant capacitors is set up. The proposed MMRM achieved improved performance compared to related resonant induction machines.

The catalytic performance on the various exposed facets has a huge difference for electrochemical nitrate reduction reactions (NO 3RR). Herein, we fabricate Co 3O 4 hexagonal nanosheets with various exposed facets, including {112}, {112}&{111}, and {111} facet. The reaction pathways of NO 3RR on various facets are elucidated via in-situ electrochemical characterizations and density functional theory (DFT) investigations. Interestingly, as the dominated facet of Co 3O 4 transform from {112} to {111}, the rate-determining step (RDS) changes from *NO 2→*NO 2H to *NO 3H→*NO 2, and the energy barrier also decreases to 0.48 eV. And {111} facet promotes the hydrogenation of NO x and NH x intermediates. Notably, Co 3O 4-{111} catalyst shows an excellent NO 3RR performance with the NH 3 yield of 5.73 mg mg cat. -1 h -1, which outperforms most of the reported activities.

Post-transplant lymphoproliferative disorder (PTLD) is a significant complication of solid organ transplantation due to the lifelong immunosuppression (IS), ranging from non-malignant lymphoproliferations to lymphomas. Plasmablastic lymphoma (PBL), a rare and aggressive lymphoma, usually presenting in immunocompromised individuals has been rarely reported in the post-transplant setting. Here we summarize the clinical and pathological features of two children with PBL and history of solid organ transplant.

Background and Purpose Alzheimer’s disease (AD), a progressive neurological disorder that causes memory decline and cognitive dysfunction, increasingly threatens human health. Rehmanniae Radix Praeparata (RRP) is derived from the steamed or wine-steamed Scrophulariaceae plant, Rehmannia glutinosa Libosch. (RR). They show promise in the treatment of AD, yet the variations in medical components and their mechanisms of action against AD remain unclear. Experimental Approach This study initially used APP/PS1 mice as AD animal models and used UPLC-QE-MS/MS, network pharmacology, proteomics, 16S rRNA sequencing to investigate differences in the medical components and mechanisms of action of RR and RRP in treating AD. Results UPLC-QE-MS/MS screening revealed that ajugol was the effective medicinal component of RR for AD treatment, and isoacteoside was that of RRP. Integrated multi-omics analyses predicted the involvement of the neuroinflammatory pathway, apoptosis pathway, and autophagy pathway in the mechanisms of the two ingredients for AD treatment. Subsequent in vivo and in vitro experiments confirmed that RR and its active component, ajugol, primarily modulated TLR/NF-κB/NLRP3 neuroinflammatory pathway and Bcl-2/Bax/Cytochrome C/Caspase-3 apoptosis pathway, whereas RRP and its active component isoacteoside predominantly affected LC3-Ⅱ/P62/p-mTOR/mTOR autophagy pathway. These components collectively improved cognitive deficits in AD mice, reduced Aβ plaque deposition in brain tissue, and diminished BV2 microglial cell cytotoxicity in the inflammation model, thereby ameliorating the progression of AD. Conclusion This study systematically elucidated the distinctions in the medical components and biological mechanisms of RR and RRP in treating AD, revealing that the unique processing of TCM is key to its efficacy.

Building on the successful synergy between biology and systems & network theories, Systems Biology and Systems Medicine have been instrumental to address complexity in the study of life sciences. Along this line, Systems Pharmacology is the obvious next step. In this review we focus on physical stimuli, whose analysis in pharmacology is generally neglected, despite their ability, once transduced, to show medicinal properties. To cope with this missed opportunity, our ambition is threefold: (i) highlight how different (mechanic, optic, magnetic, electric) physical stimuli impinge on inflammation; (ii) disseminate knowledge on cutting-edge network approaches as effective tools to exploit the intricacy and develop the potential of anti-inflammatory physical therapies within the systems pharmacology framework, to ultimately (iii) adding physical stimuli to the routine mindset of pharmacologists. We expect this review to raise more questions than it gives answers, thus igniting research in an area whose application gap urgently needs fulfillment.

An unusual case of ventral spontaneous thoracic epidural hematomaJunge ZhouDepartment of Neurosurgery, General Hospital of The Yangtze River Shipping, Wuhan Brain Hospital, Wuhan, Hubei 430010, ChinaE-mail: 43494830@qq.comTel: 15827617486Fax Number: +86-027 -82451001Patient consent: Written informed consent was obtained from the patient for the publication of this manuscript.Ethics approval: This research was approved by the ethics committee of General Hospital of The Yangtze River Shipping.Acknowledgments: We would like to thank Editage (www.editage.cn) for English language editing.Funding source: None.Conflicts of interest: None.Data access statement:  The data used to support the findings of this study have been included in this article.

In cancer, most somatic mutation are so-called passenger mutations with no functional impact on disease development. Only a subset of the mutations act as drivers and are responsible for tumor growth and progression. Identifying patient-specific driver mutations is one of the main challenges in precision oncology. Existing computational methods to identify patient-specific cancer drivers either integrate mutation and expression data with a single aggregated gene interaction network or use personalized gene interaction networks without considering mutation data. As yet, no methods making use of both patient-specific mutation and gene network data exist. For this reason, we developed PARADYS (PAtient-specific RAnking of genes driving DYSregulation in cancer), a computational tool for personalized detection and impact scoring of genes driving dysregulation in cancer (https://github.com/bionetslab/PARADYS). On several cancer cohorts, we show that PARADYS is able to make robust predictions by integrating patient-specific mutation and dysregulation data. Furthermore, PARADYS’ driver predictions allow for patient stratification into functionally coherent and biologically distinct subgroups. In particular, a case study in prostate cancer reveals a subgroup of patients with infiltration of dendritic cells in the tumor micro-environment and unexpectedly high survival times, highlighting the potential of dendritic cell therapy in prostate cancer.

Background: Cutaneous leishmaniasis (CL) is the most common clinical form of leishmaniasis that causes skin disease. Currently, there is no licensed prophylactic vaccine for CL, as the mechanisms of healing and memory T-cell responses that develop after infection with CL are far from fully understood. A review of the published articles identifying CL vaccine candidates, immuno-dominant antigens, and potent vaccine adjuvants is needed to provide comprehensive information. Therefore, we aimed to review vaccine candidates, immuno-dominant antigens, and potent vaccine adjuvants for preventing cutaneous leishmaniasis. Methods: A systematic search of published studies before December 2023 was identified using electronic databases; PubMed/MEDLINE, Hinari Research4Life, Google Scholar, and direct Google search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Data were extracted using a Microsoft Excel 2010 spreadsheet and data obtained were then reported using tables and figures and synthesized qualitatively. The quality of the included studies was assessed using the Joanna Briggs Institute’s (JBI) quality appraisal tool for experimental studies. Results: The electronic databases search yielded 661 articles of which 32 articles met the inclusion criteria. The included articles were conducted in various animal and human models and included vaccine candidates, immuno-dominant antigens, and potent vaccine adjuvants. Some of the first-generation vaccine candidates showed complete protection of the specified animal model. They induced strong T-cell mediated and antibody-mediated humoral immune responses (e.g. Curdlan dectin-1, total Leishmania antigen (TLA), and L. infantum heat shock proteins ( LiΔHSP70-II)). Almost all second and third-generation vaccine candidates, and the immuno-dominant antigens of the parasite and the host enhance T cell-mediated and antibody-mediated immune responses. We also reviewed potent vaccine adjuvants such as myrrh silver nanoparticles (MSNPs), and Imiquimod, which play an important role in enhancing immune responses against Leishmania antigens. Conclusion and recommendations: The T-cell mediated immune response was significantly induced in various experimental models (e.g. IFN-γ and TNF-α response) and also the humoral arm in some instances (e.g. IgG2). This review thus provides comprehensive information on the efficacy and induction of protective immunity of vaccine candidates, antigenic molecules, and vaccine adjuvants against CL. However, there is still a need for a comprehensive understanding of the immuno-pathogenesis of the disease upon vaccination.

Memristor crossbar-based neural networks perform parallel operations in the analog domain. Ex-situ training approach needs to program the predetermined resistance values to the memristor crossbar. Because of the stochasticity of the memristor devices, programming a memristor needs to read the device resistance value iteratively. Reading a single memristor in a crossbar (without an isolation transistor) is challenging due to the sneak path current. Programming a memristor in a crossbar to either the RON or ROFF state is relatively straight-forward. A neural network implemented using higher precision weights provides higher classification accuracy compared to a Ternary Neural Network (TNN). This paper demonstrates an implementation of memristor-based neural networks using only the two resistance values ( RON, ROFF). We have examined the impact of the device RON/ ROFF ratio, driver size on the scaling of the memristor-based neural network circuit. We have implemented a large neural network using multiple smaller 3D stacked crossbar arrays. We also have proposed novel neuron circuits to achieve higher weight precision. Our experimental result shows that the proposed higher precision synapses are easy to program and provide better classification accuracy compared to a TNN.

Limb Salvage in a Fungating Osteosarcoma; don’t give up when it’s worth trying. A case report and Literature reviewDr. Hassan Mohammed Hassan Elbahri1, Dr. Hozifa Mohammed Ali Abd-Elmaged2 , Ahmed Eltayeb Ali Hassan3, Mahmoud Alballa Almahdi Alhag4Associated Professor of orthopaedic oncology, department of orthopaedic International University of Africa-Khartoum, Sudan.Assistant Professor of orthopaedic, Alzaiem Alazhari University – Khartoum, Sudan.Teacher assistant, department of orthopaedic Alzaiem Alazhari University – Khartoum, Sudan.Teacher assistant, department of orthopaedic Alzaiem Alazhari University – Khartoum, Sudan.Corresponding Author:Ahmed Eltayeb Ali Hassan Ahmedaltayeb231@gmail.com

Synthetic biology is contributing to the advancement of the global net-negative carbon economy, with emphasis on formate as a member of the one-carbon substrate garnering substantial attention. In this study, we employed base editing tools to facilitate adaptive evolution, achieving a formate tolerance of Yarrowia lipolytica to 1 M within two months. This effort resulted in two mutant strains, designated as M25-70 and M25-14, both exhibiting significantly enhanced formate utilization capabilities. Transcriptomic analysis revealed the up-regulation of nine endogenous genes encoding formate dehydrogenases when cultivated utilizing formate as the sole carbon source. Furthermore, we uncovered the pivotal role of the glyoxylate and threonine-based serine pathway in enhancing glycine supply to promote formate assimilation. The full potential of Yarrowia lipolytica to tolerate and utilize formate establishing the foundation for pyruvate carboxylase-based carbon sequestration pathways. Importantly, this study highlights the existence of a natural formate metabolic pathway in Yarrowia lipolytica.

Environmental heterogeneity has long been assumed to promote biodiversity, but recent theory and evidence suggests substantial variability in this relationship. Here, we resolve heterogeneity’s influence on communities by considering its various facets and contextual moderators, capitalising on >3000 effects reported in 144 studies on rocky reefs worldwide. Our analyses reveal generally positive saturating or weakly humped-shaped responses of richness and abundance, with three-dimensional structure generating the strongest effects of all facets. Small-bodied and swimming organisms benefitted the most and larger-bodied benthic organisms the least, while heterogeneity also mitigated grazing and enhanced recruitment. Community responses strengthened on biogenic vs. abiotic substrates, and with environmental stress, both towards the equator and on intertidal vs. subtidal reefs. We propose that the key moderators unveiled here (heterogeneity facet, benefactor traits, and environmental stress) will more generally underpin context-dependent effects of heterogeneity on biodiversity across organismal groups and ecosystems.

We report broadband (20GHz - 40GHz) low noise amplifiers in a cascode topology using graded-channel GaN HEMTs resulting in excellent NF figure down to 1 dB with 15 dB gain per stage.

Authors:Singh M1, Ngakhusi S1, Thakur PC1, Mohanty S2, Sharma S2, Dhakal HP1Department of Pathology and Laboratory Medicine, Nepal Cancer Hospital and Research CenterDepartment of Pathology and Laboratory Medicine, Core Diagnostics, IndiaAuthors :Dr Moushami SinghMBBS, MD PathologyDepartment of Pathology and Laboratory MedicineNepal Cancer Hospital and Research CenterHarisiddhi, LalitpurBagmati Province, NepalEmail ID: moushamisingh123@gmail.comOrcid ID:Responsibilities: Manuscript reviewDr. Sajan NgakhusiDoctor of MedicineDepartment of Pathology and Laboratory MedicineNepal Cancer Hospital and Research CenterHarisiddhi, LalitpurBagmati Province, NepalEmail Id: drsajan.ngakhusi@gmail.comOrcid Id: 0009-0007-7483-3530Responsibilities: Manuscript writing, compilation of the contents, and manuscript reviewingDr Prabhat Chandra ThakurMBBS, MS(ORL-HNS), Fellowship Head & Neck OncologyDepartment of Head and Neck Oncology UnitNepal Cancer Hospital and Research CenterHarisiddhi, LalitpurBagmati Province, NepalEmail ID: thakurprabhat@hotmail.comOrcid ID: 0000-0002-2750-0596Responsibilities: Clinical and physical examination details and manuscript reviewDr. Sambit MohantyMBBS, MD PathologyDepartment of Pathology and Laboratory MedicineCore Diagnostics, IndiaEmail ID: sambit.mohanty@corediagnostics.inResponsibilities: Immunohistochemistry reporting and manuscript reviewDr. Shivani SharmaMBBS, MD PathologyCore Diagnostics, IndiaEmail Id: shivani.sharma@corediagnostics.inResponsibilities: Immunohistochemistry reporting and manuscript reviewDr Hari Prasad Dhakal, MBBS, MD, PhD Senior Consultant Pathologist Chairperson, Institutional Review Committee NCHRC Deputy Director, Academic & Research Division Head, Department of Pathology and Laboratory Medicine Member, Infection Prevention & Control Committee Member, Clinical Governance Committee Nepal Cancer Hospital and Research Center Harisiddhi, Lalitpur, Nepal Email: drhari.dhakal@nch.com.npResponsibilities: Manuscript review

Title PageA Novel Approach for Complex Enteroatmospheric Fistula Treatment: Double Catheterization Cannula Combined with Biologic Mesh and Flap Transplantation

IntroductionHydatid cyst is caused by infection with a parasite belonging to theEchinococcus family. Humans are the intermediate host of this disease and get infected directly or indirectly after the parasite eggs enter the digestive system. According to the WHO, it is considered a neglected disease world-wide, as it still remains highly prevalent despite the improvement of public health and following sanitary protocols by humans (1,2). This disease is mostly asymptomatic and is incidentally detected (3). Usually, only one cyst is formed during infection, and the formation of several cysts and the involvement of several organs is not common. The most commonly involved organ is the liver, followed by the lung. The involvement of other organs is much less common, and the involvement of the peritoneum and omentum is very rare, and is usually caused by abdominal trauma, the rupture of a cyst in the liver or other organs, and the release of parasites leading to the contamination of the abdominal space (4). In this study, we introduce a case of hydatid cysts in liver, spleen and peritoneum, in which the radiological appearance and clinical symptoms had raised high suspicion of abdominal malignancy and peritoneal seeding.

Cyclopenta-fused B2N2-pyrene (B2N2CP) and diazaborepin (NBNM) have been accomplished from a same bi-indoles pre-cursor in three steps. Borylative cyclization of bi-indoles precursor with 2.0 equiva-lents BCl3 afforded NBNM as the major product, whereas increasing the BCl3 to 3.0 equivalents deliv-ered B2N2CP as the major product. Both B2N2CP and NBNM are highly emissive in solution. B2N2CP emit in deep blue region, while NBNM emit in the region of blue to green. Moreover, we found that flu-oride anion addition to the solution of B2N2CP and NBNM led to great change of their absorption and emission spectra.

We have developed an efficient synthetic route of parental ullazine in three steps from commercially available synthons with overall yield of 53%. The single crystal X-ray structure of parental ullazine was studied in detail. Parental ullazine core can be functionalized either by late-stage Vilsmeier-Haack formylation/condensation sequence or by C-N cross-coupling with a pre-installed bromine. Pre-liminary results show that the condensation of CHO-substituted ullazine (U-CHO) gave a novel imidazole substituted ullazine. The brominated ullazine (U-Br) can undergo Buchwald-Hartwig cross-coupling smoothly, resulting a carbazole substituted ullazine. In ad-dition, parental ullazine showed redshifted absorption and emission spectra as compared to its isoelectronic isomer pyrene, and no excimer formation in higher concentration.

A document by Moushami Singh. Click on the document to view its contents.

Fire plays a pivotal role in driving ecological shifts between Mediterranean-type vegetation and subtropical ecosystems in South Africa. This study investigates long-term environmental dynamics and ecological regime changes at the Mediterranean-type vegetation /subtropical boundary using a 6000-year palaeoecological sequence from the Baviaanskloof – a region of South Africa characterized by high levels of biodiversity and climate dynamism. Combining fossil pollen and microcharcoal data from a rock hyrax (Procavia capensis) midden, we analyse vegetation responses to environmental changes. Our findings reveal that Mediterranean-type vegetation resilience prevailed until ca. 2800 cal yr BP when a major fire event triggered a transition to a subtropical thicket-dominated environment. This abrupt ecological turnover underscores the significance of fire as a major driver of vegetation change at the Mediterranean-type vegetation /subtropical boundary. Our study emphasizes the vulnerability of Mediterranean-type vegetation ecosystems to global environmental change, suggesting potential implications for similar biome boundaries worldwide. By integrating multi-proxy palaeoecological evidence, we gain insights into the resilience and vulnerability of these ecosystems, aiding in understanding future responses to climate change scenarios.

Purpose: The effective treatment of chronic myeloid leukemia (CML) remains a challenge due to non-adherence to Imatinib. We aimed to assess the factors associated with non-adherence to Imatinib therapy in newly diagnosed patients with CML. Methods: Eighty-two adult patients initiating Imatinib were recruited. Adherence was measured using medication possession ratio (MPR) and visual analogue scale (VAS) at 90 days. Demographic, clinical and quality-of-life variables were assessed at baseline. Pearson’s correlation and linear regression analyses were performed to identify associations and independent predictors of non-adherence respectively. Results: Twenty-two percent (18/82) of patients were non-adherent (MPR ≤ 85). Self-reported adherence via VAS correlated significantly with MPR. Among various factors, cognitive function score and occurrence of adverse drug event (ADR) were associated with adherence. The impact of disease on daily-life score was negatively associated with adherence. The independent predictors of adherence were role function score and impact of disease on mood score. Conclusions: This study identified cognitive and role function, impact of disease on daily life and mood and occurrence of ADR as variables influencing non-adherence to Imatinib in CML patients. Early identification of these factors can guide interventions to improve adherence and treatment outcomes.

Objective:Currently, there is no established preoperative evaluation standard for direct hysterectomy in CINIII patients who are unable to undergo conectomy.We have developed a nomogram that can be used to predict surgical modalities for initial treatment of CINIII after menopause,and estimated the performance of the nomogram by internal validations. Design：Case-control design within retrospective study. Setting：Shengjing Hospital of China Medical University. Population or Sample：A total of 454 postmenopausal participants diagnosed with CINIII. Methods: Group A and group B were divided into two cohorts based on different initial treatment modalities. Group A underwent direct hysterectomy (88 cases), while group B underwent conization followed by hysterectomy (366 cases). Based on the postoperative pathological findings, the patients were categorized into the upgraded pathological grope (105 cases, with 8 in group A and 97 in group B) and the non-upgraded pathological grope (349 cases, with 80 in group A and 269 in group B).Multiple logistic regression analysis was used to identify predictors and establish nomogram.The performance of the nomogram was evaluated by using the area under the curve (AUC),calibration curve and the decision curve analysis(DCA). Main Outcome Measures：Pathological upgrade. Result:The independent risk factors identified in this study include menopause years,post-coital bleeding, HPV16/18 infection,cervical lesion counts, SCCAg and TCT (P<0.05). The six indicators were used to create a nomogram for predicting pathological upgrade. The training set yielded an AUC of 0.959 (95% confidence interval [CI], 0.936-0.982), while the validation set showed an AUC of 0.850 (95% CI, 0.775-0.926).The nomogram was well-calibrated.The DCA results demonstrate a higher net gain value. Conclusion：The nomogram model predicts postoperative cervical cancer risk in postmenopausal CINIII patients based on menopause years, HPV16/18 positivity, TCT results, SCCAg levels, cervical lesion counts, and post-coital bleeding. In cases of low risk, direct hysterectomy may be considered as initial treatment. Our scoring system offers safer and more efficient treatment options for patients.

In this paper, we compute a new hybrid mean sea surface (MSS) model by merging three recent models, CNES_CLS22, SCRIPPS_CLS22 and DTU21, and taking advantage of their respective features. The errors associated with these models were assessed using sea level anomalies for wavelengths ranging from 15 to 100km from Sentinel-3A (S3A), SWOT KaRIn during its calibration phase and ICESat-2 in the Arctic ice-covered regions. The absolute error associated with this new Hybrid23 MSS is estimated at 0.15 ± 0.04 cm² with S3A. The greatest improvements observed on S3A sea level anomalies are mainly located in coastal regions and along geodetic structures: on average, the error is reduced by 23% within 200km along the coast and by 35% in the Indonesian region compared with SCRIPPS_CLS22. Despite these improvements, the MSS error still impacts significantly sea level anomalies computed from altimetry: it explains 15% and 18% of the S3A and SWOT KaRIn respective global variance. It becomes predominant (> 30%) if we consider the shorter wavelengths ([15, 30km]). CNES_CLS15, older, explains up to 88% of the variance of SWOT KaRIn at these wavelengths. MSS errors have become a major limiting factor to the accuracy of sea level anomalies, and hybridization even adds sub-mesoscale errors. SCRIPPS_CLS22 and DTU21 also remain better in certain regions of the North Atlantic above 60°N and in Arctic coastal areas. Finally, many efforts are still required to develop the MSS to a new level of precision, which we could soon achieve with SWOT KaRIn during the scientific phase.