MYH9-related disorders (MYH9-RD) are the leading cause of inherited thrombocytopenia（IPD）. This autosomal-dominant macrothrombocytopenia syndrome consisted of the May-Hegglin anomaly, Fechtner syndrome, Sebastian syndrome, and Epstein syndromes. To date， hematopoietic stem cell transplantation (HSCT) is the only curative therapy for congenital thrombocytopenias, such as Wiskott-Aldrich syndrome(WAS) and Glanzmann thrombasthenia (GT). However, no relevant literature reported on the outcome of MYH9-related disorders. We first described a pediatric MYH9-RD patient who underwent a successful myeloablative allogeneic HSCT with umbilical cord blood stem cells resulting in complete resolution. Now one year passed after HSCT. The patient’s condition remained stable during the follow-up. This case highlights the implications of curative therapy of HSCT in MYH9-RD patients.

The strong core base in chemical engineering during the latter half of the 20th century enabled chemical engineers to contribute extensively to many areas outside of the traditional. The depth of such involvement has led researchers to confront questions much more engaging to the field of application, thus adopting and cultivating expertise more native to it than to secure chemical engineering as a discipline. The progress of knowledge in science and engineering must leave a strong trail of fundamental understanding through developed methodologies that can assist in continuing progress. If this tenet is acknowledged, this article yields considerable scope for discussion on whether chemical engineering research is continuing to provide for a growing core that has endowed chemical engineers with the ability to formulate and solve important societal problems in which material systems undergo changes in composition and energy. We discuss opportunities for hopefully serving the issues of concern.

Severe SARS-CoV-2 infections in pediatrics are rare and usually presented as multisystem inflammatory syndrome in children. There are few descriptions about pediatric oncology patients. We describe a case of 5-year-old male with acute myeloid leukemia. He presented febrile neutropenia with skin lesions and progressive clinical worsening. He had positive RT-PCR test for SARS-CoV-2 and criteria for MIS-C. He received methylprednisolone, immunoglobulin and granulocyte-colony-stimulating factor. Anti-interleukin 6 was administrated due to severe lung disease and refractory to treatment, presenting response and slow clinical recovery. Chemotherapy was restarted, he didn't present relapse during treatment and has no sequelae of COVID-19.

Background: Fibroids are benign tumors in women of reproductive age and associated with hormonal, genetic and molecular variables. Objectives: To search for the mechanisms by which vitamin D influences the development of fibroids. Search strategy: Electronic databases were searched from January 2009 to October 2019. The Internet search tool includes the PUBMED, COCHRANE and EMBASE search engines. Of these, scientific articles, meta-analyses, therapeutic guidelines, reviews, and research articles were consulted, as well as the most recent guidelines on the subject, according to the Brazilian Society of Gynecology. Selection criteria: The inclusion criteria were publications in the last ten years in English, Portuguese, and Spanish; publications that met the proposed objective described in PICO: a. Randomized trials; B. Observational studies (including cohort and case-control studies). Exclusion criteria included: articles published before 2010; languages other than English, Portuguese, and Spanish; articles that did not meet the research objectives; ongoing studies and abstracts. Data collection and analysis: The selected studies were divided according to the type of study and divided into: 1. Newcastle-Ottawa Scale-Case-Control Studies and Cohort Studies; 2. COCHRANE manual for systematic intervention reviews. Main results: 12 out of 15 studies were non-randomized studies (80%) with Kappa values above six. Kappa agreement was 0.615, suggesting good or substantial agreement. Conclusion: Vitamin D (1,25(OH)2 D3) plays a significant role in cell growth control, programmed cell death, and DNA damage. Low levels of Vitamin D seem to be an important factor, direct or indirectly, in the etiopathogenesis of uterine fibroids.

Objective: To compare patients undergoing laparoscopic sacrocolpopexy for pelvic organ prolapse POP, in terms of sexual function and surgical anatomical outcomes more than 5-years follow up period. Design: This is a cohort study of prospectively collected data that includes all women who underwent LSC between July 2005 and December 2021 at a tertiary care center. Setting: Improvement in sexual function is an acknowledged goal for women undergoing pelvic organ prolapse repair. The impact of POP surgeries on sexual activity and function is very controversial, with some studies showing improvement, while others showed no differences or worsening in sexuality after the surgery Population: 228 women were enrolled in this study. Methods: Patients completed the validated quality of life questionnaires and were evaluated using the POP-Q, the PFDI-20, PFIQ-7 and the PISQ-12 scores. Patients were divided preoperatively according to their sexual activity and postoperatively according to the sexual improvement after POP surgery. Main Outcomes: To compare the PISQ-12 score pre and postoperatively and to assess anatomical and sexual improvement after surgery. Results: There was a statistically significant improvement in the PFDI, PFIQ and POPQ-score score. There was no significant improvement in the PISQ-12 score with more than 5 years follow-up. 76.1% of patients who were not sexually active preoperatively resumed their sexual activity after the surgery. Conclusions: The anatomical correction of a pelvic organ prolapses and pelvic floor disorders by laparoscopic sacrocolpopexy may improve sexual function but did not change significantly the sexuality score. Funding: No funding. Keywords: prolapse, sacrocolpopexy, laparoscopy, sexuality.

Objective: The relationships of ‘ingredient-target-pathway’ and hypoglycemic effect of Scutellariae Radix (SD) in the treatment of diabetes were explored using network pharmacology, molecular docking and animal experiments. Methods: SD and its targets were identified using network analysis followed by experimental validation. First, the Tcmsp and Drugbank databases were mined for the targets of SD and diabetes, and the intersection target genes were screened. The key targets and enriched pathways were examined by Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. SD main active components, target genes and KEGG networks were created by Cytoscape software. The correspondence between SD components and targets was verified by molecular docking. Finally, animal experiments were carried out to confirm the hypoglycemic effect of SD. Results: The 22 intersection targets were confirmed for the hypoglycemic effect of SD. GO analysis showed that 18 biological processes, 9 cellular components and 15 molecular functions were identified (P ≤ 0.01). Eighteen related signaling pathways were identified by KEGG analysis (P ≤ 0.05). Molecular docking results indicated that the targets of diabetes bound strongly to the main components of SD. Animal experiments showed that SD could decrease the blood sugar of diabetic rats to normal level. Conclusion: The present study explored the potential targets and signaling pathways of SD on diabetes. The results may help to illustrate the hypoglycemic mechanism (s) of SD.

Understanding the ecological and evolutionary links between stages in complex life histories is an important goal of biology, but studies differ greatly in their approach. Some studies follow individuals across their life history (“individual longitudinal”), while others follow cohorts (“cohort longitudinal”)—each have their strengths and weaknesses. Our understanding of links among life-history stages probably depends on the approaches we use, but we have no estimates of their relative prevalence. Using marine invertebrates as a model, we used a formal, systematic literature map to screen 17,000+ papers studying complex life histories. For 3,315 experiments from 1,716 articles, we characterised the study type, (i.e. cohort longitudinal, individual longitudinal or single stage) as well as other factors. Individual longitudinal studies are extremely rare, accounting for just 1.7% of studies. Clearly much progress has been made, but to fully understand the links among life-history stages, more individual longitudinal studies are necessary.

Many authors have noted the apparent “decoupling” of the taxonomic and ecological severity of mass extinction events, with no widely accepted mechanistic explanation for this pattern having been offered. Here we test between two key factors that potentially influence ecological severity: biosphere entropy (a measure of functional redundancy), and the degree of functional selectivity (in terms of deviation from a pattern of random extinction with respect to functional entities). Our results demonstrate that while the Shannon entropy of the biosphere prior to a mass extinction event determines the expected outcome following a major perturbation of a given magnitude, variation in biosphere structure between major extinction intervals is insufficient to explain the observed variation in ecological severity. Within this information-theoretic framework, we show that it is the degree of functional selectivity which is expected to primarily determine the ecological impact of a given perturbation when biosphere entropy is not substantially different.

Roosts are vital for the survival of many species, and how individuals choose one site over another is affected by various ecological factors. Biomechanical constraints could also affect roost selection, particularly in volant taxa that require sites with easy access, thereby reducing costs (i.e., predation, accidents). To date, no studies have established an association between landing performance and roost-site selection, as predicted by biomechanical constraints associated with flight. We aim to determine roost-site selection in disc-winged bats (Thyroptera tricolor), a species known to roost within developing tubular leaves. This study is coupled with various experiments that measure how a conspicuous apex affects landing tactics and performance. We show that T. tricolor prefers leaves with a longer apex, the space typically used for landing. Bats also approach and enter these leaves more consistently, increasing task performance while reducing the risk of injuries.

Here, we report a case of acute liver failure and a drastic increase of liver enzyme in a pediatrician with COVID-19 infection without a history of preexisting liver disease. Unfortunately, the patient passed away several days after intensive care unit (ICU) admission.

In the current study, an effective numerical technique is presented for solving a class of three-dimensional fractional differential-integral equations via the three-dimensional block-pulse functions. The Caputo fractional derivative is applied to deal with the fractional derivative terms, and the differential operational matrices of 3D-BPFs are utilized to transform the original system. In the end of the paper, two numerical examples are presented to verify the proposed method.

The dynamic transitions of the Brusselator model has been recently analyzed in Y. Choi et’al (2021) and T. Ma, S. Wang (2011). Our aim in this paper is to address the relation between the pattern formation and dynamic transition results left open in those papers. We consider the problem in the setting of a 2D rectangular box where an instability of the homogeneous steady state occurs due to the perturbations in the direction of several modes becoming critical simultaneously. Our main results are two folds: (1) a rigorous characterization of the types and structure of the dynamic transitions of the model from basic homogeneous states and (2) the relation between the dynamic transitions and the pattern formations. We observe that the Brusselator model exhibits different transition types and patterns depending on the nonlinear interactions of the pattern of the critical modes.

Background and Purpose Lapatinib, a widely-used dual inhibitor of EGFR/ERBB1 and HER2/ERBB2 effectively targeting HER2 positive breast cancer, has been seriously limited due to cutaneous toxicity. However, the specific mechanism of lapatinib-induced cutaneous toxicity has not been clarified, leading to a lack of effective strategy targets to improve clinical safety. Here, we aimed to identify molecular mechanism occurs in this process and strive for effective intervention strategies against lapatinib-induced cutaneous side effects. Experimental and Approach C57BL/6 mice were subjected to lapatinib via intragastric administration, serum was used for ELISA assay, skin tissue was collected and performed with histopathological analysis. Apoptotic assay was analyzed in HaCaT and NHEK cell lines, comet assay was conducted to measure the damage of DNA, real-time PCR was used to assess the level of HMGB and inflammatory factors. Key Results We found that lapatinib could induce mitochondrial dysfunction, lead to DNA damage and finally cause apoptosis of keratinocytes. In addition, we found that lapatinib could induce aberrant immune response and promote the release of inflammatory factors in vitro and in vivo. Mechanistically, downregulated expression of HMGB1 played a critical role in these toxic reaction processes. Delightfully, we found that saikosaponin A could significantly rescue the reduced HMGB1 transcription, which could alleviate lapatinib-induced DNA damage, inhibit keratinocyte apoptosis and further prevent toxicity of lapatinib in mice. Conclusion and Implications Our study provided molecular mechanism of lapatinib-induced cutaneous toxicity, and shed new light on the prevention of cutaneous adverse drug reactions induced by EGFR inhibitors.

Abstract: Mathematics plays an irreplaceable role in human historical development and social life. Mathematics is a universal means for human beings to strictly describe the abstract structures and patterns of things, and can be applied to any problem in the real world. Therefore, the same applies to legal issues in the social sciences. In the field of intellectual property law, where law and science and technology are relatively closely integrated, the substantive similarity of audio-visual works has always been in qualitative analysis, while the increasingly perfect rule of law society and the increasingly high-speed commercial activities require legal work to be provided under the premise of stability. The boundary between number and quantity is clear. At this time, the Ministry of Education proposed to promote the construction of new liberal arts education. As a basic subject of natural science, mathematics, of course, should be at the forefront of subject integration. Mathematics’ solution to problems is nothing more than direct arithmetic solution, and indirect transformation (transformed into currently solvable) solution. At the same time, with the introduction and development of the concept of computational law in the field of law, the past tense of computational law and the development of computational law should have its own development results.

Background: Totally implantable venous access devices (TIVADs) are frequently used in pediatric patients with cancer owing to their multiple benefits. Despite occasional infections with TIVADs, knowledge of the incidence and risk factors is limited. Methods: This retrospective study included pediatric patients with cancer who received TIVAD at Chungbuk National University Hospital from 2001 to 2018. We collected data on demographics, diagnosis, duration of TIVAD use, pathogens, and other risk factors. Results: During the study period, 47 TIVADs with 20,770 device-days were applied in 42 patients. There were 14 TIVAD infections (14/47, 29.8%), with an infection rate of 0.25 infections per TIVAD per year (0.69 cases/1000 device-days). TIVAD infections occurred at a median of 5.5 months (range, 8 days–30 months) after insertion. The most common causative microorganisms were methicillin-resistant coagulase-negative staphylococci (n = 8, 57.1%) followed by Escherichia coli and Streptococcus mitis (n = 2, each). A platelet count below 150,000/μL at the time of TIVAD insertion and diagnosis of acute lymphoblastic leukemia (ALL) were the major risk factors for TIVAD infection. Device removal was the mainstay of treatment (11/14, 78.6%). Conclusion: TIVAD insertion was safe and dependable in children with malignancies. Risk factors for TIVAD infection included a platelet count below the normal range at the time of device insertion and a diagnosis of ALL. Further studies are needed to identify preventive factors against TIVAD infections in children with cancer.

Acanthogobius ommaturus is a large, economically important annual fish widely distributed in coastal and estuarine areas. The adults will die after breeding, and its life cycle is only one year. The first chromosome-level genome assembly of A. ommaturus was obtained by PacBio and Hi-C sequencing in this study. The final genome assembly after Hi-C correction was 921.49 Mb, with contig N50 and scaffold N50 values of 15.70 Mb and 40.99 Mb, respectively. The assembled sequences were anchored to 22 chromosomes by using Hi-C data. A total of 18,752 protein-coding genes were predicted, 97.90% of which were successfully annotated. A. ommaturus is phylogenetically closely related to Periophthalmodon magnuspinnatus, Boleophthalmus pectinirostris, diverging approximately 31.9 million years ago with the two goby species. The A. ommaturus genome displayed 597 expanded and 3,094 contracted gene families compared with the common ancestor. A total of 1155 positive selected genes (PSGs) (p < 0.05) were identified. Based on comparative genomic analyses, we obtained several expanded genes such as ACSBG2, LRP1, LRP6 and ZNF638 involved in lipid metabolism. Totally twenty candidate genes were identified under positive selection, which associated with lifespan including ERCC6, IGF1, POLG, and TERT. Interspecific collinearity analysis showed a high genomic synteny between A. ommaturus and Periophthalmodon magnuspinnatus. The effective population size of A. ommaturus decreased drastically during 200-100Ka because of Guxiang ice age, then increased gradually following warm periods. This study provides pivotal genetic resources for in-depth biological and evolutionary studies, and underlies the molecular basis for lipid metabolism.

DNA metabarcoding necessitates labelling amplicons in order to connect sequencing reads with samples, but labelling protocols may cause errors where indexes are incorrectly assembled during PCR due to tag-jumping. A recent paper by Bohmann et al (2021) reviews the main labelling methods and point out that library building using PCR’s on tagged amplicons may be particularly problematic. Due to unforeseen problems in two sequencing projects, we had to use a second PCR on tagged amplicons to salvage two large data sets. This test showed that the problems with tag-jumping errors were acceptable and could be accounted for during analysis, if handled properly when designing the indexing strategy.

ABSTRACT Background and Purpose The pulmonary vascular remodeling (PVR), the pathological basis of pulmonary hypertension (PH), entails pulmonary artery smooth muscle cells (PASMCs) phenotypic switching, but appreciation of the underlying mechanisms is incomplete. Exosomes, a novel transfer machinery enabling delivery of its cargos to recipient cells, have been recently implicated in PH. The two critical questions of whether plasma-derived exosomes drive PASMCs phenotypic switching and what cargo the exosomes transport, however, remain unclear. Experimental Approach PH is induced by exposure of rats to chronic hypoxia (10% O2, 3 weeks). Exosomes were isolated and purified from rat plasma by ultracentrifugation. Exosomal LOX-1 was assessed by transmission electron microscopy and Western blotting. PASMCs phenotypic switching was determined by Western blotting, immunofluorescence staining and flow cytometry. Key Results We characterized lectin like oxidized low-density lipoprotein receptor-1 (LOX-1) as a novel cargo of plasma-derived exosomes in PH. With LOX-1 knockout (Olr1-/-) rats-derived exosomes, we demonstrated that exosomal LOX-1 could be transferred into PASMCs and thus elicited cell phenotypic switching. Of importance, Olr1-/- rats exhibited no cell phenotypic switching and developed less severe PH, but administration of wild type rather than Olr1-/- exosomes to Olr1-/- rats recapitulated the phenotype of PH with robust PASMCs phenotypic switching. We also revealed that exosomal LOX-1 triggered PASMCs phenotypic switching, PVR and ultimately PH via ERK1/2-KLF4 signaling axis. Conclusion and Implications This study has generated proof that plasma-derived exosomes confer PH by delivering LOX-1 into PASMCs. Hence, exosomal LOX-1 represents a novel exploitable target for PH prevention and treatment.

Confused geographical-structure of population and mito-nuclear discordance have been shaped by a combination of rapid population demographic changes and ecological shifts. In this study, we generated a time calibrated phylogeny of Scutiger boulengeri, an endemic Tibetan alpine toad occurring in mountain streams in Qinghai-Tibet Plateau, based on three mitochondria (mtDNA) genes, in which eight clades were assigned into three deeply divergent lineages. While nuclear DNA (nuDNA) revealed three distinct clusters without geographical structure indicating significantly high rates of gene flow by population structure analysis. The coalescent theory framework (approximate Bayesian computation model DIYABC and Migrate-N) suggested that the intraspecific main clusters divergence was the result of hybridization after secondary contact in Holocene around 0.59 Ma, with population size change. The ratio of mtDNA divergence to nuDNA divergence was 2.3, less than 4, failed to test a sex-biased dispersal. Geographic cline analysis showing a wide hybrid zone initially established in southwestern China, without significant reproductive isolation but a strong influence of introgression in S. boulengeri, suggested high fitness of hybrids. Moreover, mtDNA exhibited isolation by distance (IBD) while nuDNA showed significant isolation by environment (IBE). Our results suggested such mito-nuclear discordance might have been first caused by geographic isolations, followed by hybridization mediated by precipitation, and produced a wide hybrid zone, which contributed to confused geographical-structure of the nuDNA in S. boulengeri. This study unveiled the complicated historical process that might have led to specific genetic pattern and specific climate factor facilitating phenotypic diversity in this system.

Production and consumption of Nile tilapia (Oreochromis niloticus) have been growing. Insulin like growth factors-1(IGF-1) is a hormone that affects the weight of animals. To produce high-quality Nile tilapia, traditional breeding combined with molecular marker technology to assist selective breeding has long become an effective means of cultivating new fish strains. Moreover, molecular markers or genes related to important economic traits can be found with the help of molecular-assisted selection breeding. A total of 152 fish fin samples were collected from Janghang Fishing Ground and classified according to their weight and sex (good male-35, bad male-35, medium male-12, good female-35, and bad female-35). A total of 9 SNPs (single nucleotide polymorphism) of Nile tilapia IGF-1 were identified in this study, One SNP is in the promoter, three SNPs are in the 5’UTR, and five SNPs are in the 3’UTR. By analyzing the correlation between body weight and GBs, effective GBs were selected. This study aims to improve the Nile tilapia species with the help of molecular markers in the future and to select fast-growing new strains, shorten the breeding cycle, achieve maximum economic benefits, and realize the important economic traits of tilapia. The best combination and strengthened tilapia breeding technology system provides a reference for molecular genetics. It also provides a guarantee and basis for future human protection of species diversity, food and nutrition safety, and selection of high-quality species breeding.

In the last two years, SARS-CoV-2 infection, commonly called COVID-19, has taken a jump from being rarely talked about to becoming a household name. Making it to history as the 5th global pandemic, this public health crisis has taken millions of lives all over the world. Right from the time of identification of patient zero, the pandemic has been a series of waves of infection, causing a domino effect whose impact has been felt in all walks of life. Global efforts have been underway to combat this pandemic and minimize its repercussions, resulting in the development of efficient vaccines and drugs to control and treat the disease. However, making the benefits of these efforts available to everyone and walking the path towards the end of the pandemic remains a challenge. Keeping this in view, this review intends to present aspects of sequential development of the pandemic, different types of variants, risks associated with different categories of population, drugs currently in use, recent advancements in diagnostics and treatment, and the challenges that continue to remain in overcoming this pandemic. However, the task of controlling and managing the impact of such a massive pandemic goes well beyond the boundaries of what present-day technology in the field of medicine and health-care can offer. A collaborative and integrative approach between academic, scientific, social, and economic factors, along with close supervision and reinforcement of the current public safety protocols, can help to ensure a better management strategy to control the progression of COVID-19.

The classic findings of vitamin B12 deficiency include anemia and neurologic symptoms. Elevation of liver enzymes is an atypical finding of this deficiency. In this case report, we present a ten-year-old male with pancytopenia due to vitamin B12 deficiency which was associated with elevated transaminases. Extensive work-up was completed to find a cause for this transaminitis with unremarkable results. Liver enzyme levels normalized with aggressive intramuscular vitamin B12 supplementation, suggesting a direct correlation.

IgA pemphigus is a rare autoimmune neutrophil predominant blistering associated with IgA autoantibodies. The condition most commonly presents as annular vesiculopustular plaques on the trunk, extremities, and intertriginous regions. SPD may be associated with an underlying gammopathy such as multiple myeloma.

In this paper, it is discussed that the oil-gas wells of mining construction penetrates the geothermal reservoirs system cap rocks and a lot of geothermal energy lost lead to the floor heating effect in fossil energy mining processes, and its importance to global climate change. It is also illustrated that the interrelationship among fossil energy mining, deep geotemperature rise and abyssal ocean warming. Thus it expresses the significance of energy mining affecting environmental ecosystem and climate change in globe.