Surface chemistry engineered selenium nanoparticles as bactericidal and immuno-modulating dual-functional agents for combating methicillin-resistant Staphylococcus aureus Infection.

Because of the extremely complexed microenvironment of drug-resistant bacterial infection, nanomaterials with both bactericidal and immuno-modulating activities are undoubtedly the ideal modality for overcoming drug resistance. Herein, we precisely engineered the surface chemistry of selenium nanoparticles (SeNPs) using neutral (polyvinylpyrrolidone-PVP), anionic (letinan-LET) and cationic (chitosan-CS) surfactants. It was found that surface chemistry greatly influenced the bioactivities of functionalized SeNPs, their interactions with methicillin-resistant Staphylococcus aureus (MRSA), immune cells and metabolisms. LET-functionalized SeNPs with distinct metabolisms exhibited the best inhibitory efficacy compared to other kinds of SeNPs against MRSA through inducing robust ROS generation and damaging bacterial cell wall. Meanwhile, only LET-SeNPs could effectively activate natural kill (NK) cells, and enhance the phagocytic capability of macrophages and its killing activity against bacteria. Furthermore, in vivo studies suggested that LET-SeNPs treatment highly effectively combated MRSA infection and promoted wound healing by triggering much more mouse NK cells, CD8+ and CD4+ T lymphocytes infiltrating into the infected area at the early stage to efficiently eliminate MRSA in the mouse model. This study demonstrates that the novel functionalized SeNP with dual functions could serve as an effective antibacterial agent and could guide the development of next generation antibacterial agents.

The telomere-to-telomere (T2T) genome of Peucedanum praeruptorum Dunn provides insights into the genome evolution and coumarin biosynthesis.

BACKGROUND: Traditional Chinese medicine has used Peucedanum praeruptorum Dunn (Apiaceae) for a long time. Various coumarins, including the significant constituents praeruptorin (A-E), are the active constituents in the dried roots of P. praeruptorum. Previous transcriptomic and metabolomic studies have attempted to elucidate the distribution and biosynthetic network of these medicinal-valuable compounds. However, the lack of a high-quality reference genome impedes an in-depth understanding of genetic traits and thus the development of better breeding strategies. RESULTS: A telomere-to-telomere (T2T) genome was assembled for P. praeruptorum by combining PacBio HiFi, ONT ultra-long, and Hi-C data. The final genome assembly was approximately 1.798 Gb, assigned to 11 chromosomes with genome completeness >98%. Comparative genomic analysis suggested that P. praeruptorum experienced 2 whole-genome duplication events. By the transcriptomic and metabolomic analysis of the coumarin metabolic pathway, we presented coumarins' spatial and temporal distribution and the expression patterns of critical genes for its biosynthesis. Notably, the COSY and cytochrome P450 genes showed tandem duplications on several chromosomes, which may be responsible for the high accumulation of coumarins. CONCLUSIONS: A T2T genome for P. praeruptorum was obtained, providing molecular insights into the chromosomal distribution of the coumarin biosynthetic genes. This high-quality genome is an essential resource for designing engineering strategies for improving the production of these valuable compounds.

Survey results of COVID-19 pandemic on female surgical trainees: New normal work environment.

BACKGROUND: The COVID-19 pandemic has had a profound impact on surgical training globally. We aimed to explore and identify the specific challenges faced by women surgeons during the pandemic and provide recommendations for improvement. METHODS: A survey was conducted among trainee members of the Association of Women Surgeons, assessing various aspects of clinical training, mental well-being, and personal and professional life. RESULTS: The respondents were distributed across the United States, with the majority (28%) from the Midwest and Northeast. Training settings were predominantly academic university hospital programs (85%). The majority (92%) were resident trainees and 32% were in research. General surgery, constituting 86% of the respondents, was the most common specialty. There was a decline in surgical cases, research, mental health, and quality of didactics. Limited learning opportunities and challenges in job search were reported. Although virtual conferences were deemed affordable, the lack of networking was noted to be significant. CONCLUSION: The study highlights the need for ongoing support and adaptation in surgical training programs. These programs include the optimization of virtual platforms, prioritizing mental well-being, and ensuring equal opportunities. Strategies to mitigate the impact of future disruptions and promote gender equality are essential. Further research and workflow changes are warranted for effective capacity building.

The male reproductive toxicity after 5-Fluorouracil exposure: DNA damage, oxidative stress, and mitochondrial dysfunction in vitro and in vivo.

5-Fluorouracil (5-FU), a chemotherapeutic drug used to treat a variety of cancers, can enter the environment through different routes, causing serious public health and environmental concerns. It has been reported that 5-FU exposure adversely affects male reproductive function, and its effects on this system cannot be avoided. In this study, using western blotting and quantitative polymerase chain reaction studies, we found that 5-FU promoted testicular injury by inducing oxidative stress, which was accompanied by the inhibition of nuclear factor erythroid 2-related factor 2/antioxidant response element signaling. Accumulation of reactive oxygen species (ROS) aggravated 5-FU-mediated mitochondrial dysfunction and apoptosis in murine cell lines and testes, indicating oxidative stress and mitochondrial-dependent apoptotic signaling play crucial roles in the damage of spermatogenic cells caused. N-Acetyl-L-cysteine, an antioxidant that scavenges intracellular ROS, protected spermatogenic cells from 5-FU-induced oxidative damage and mitochondrial dysfunction, revealing the important role of ROS in testicular dysfunction caused by 5-FU. We found that 5-FU exposure induces testicular cell apoptosis through ROS-mediated mitochondria pathway in mice. In summary, our findings revealed the reproductive toxicological effect of 5-FU on mice and its mechanism, provided basic data reference for adverse ecological and human health outcomes associated with 5-FU contamination or poisoning.

Interfacial OOH* mediated Fe(II) regeneration on the single atom Co-N-C catalyst for efficient Fenton-like processes.

Fe(II) regeneration is decisive for highly efficient H2O2-based Fenton-like processes, but the role of cobalt-containing reactive sites in promoting Fe(II) regeneration was overlooked. Herein, a single atom Co-N-C catalyst was employed in Fe(II)/H2O2 system to promote the degradation of diverse organic contaminants. The EPR and quenching experiments indicated Co-N-C significantly enhanced the generation of superoxide species, and accelerated hydroxyl radical generation for pollutant degradation. The electrochemical and surface composition analyses demonstrated the enhanced H2O2 activation and Fe(III)/Fe(II) recycling on the catalyst. Furthermore, in-situ Raman characterization with shell-isolated gold nanoparticles was employed to visualize the interfacial reactive intermediates and their time-resolved interaction. The accumulation of interfacial CoOOH* was confirmed when Co-N-C activated H2O2 alone, but it rapidly transformed into FeOOH* upon Fe(II) addition. Besides, the temporal variation of OOH* intermediates and the relative intensity of Co(III)-O and Co(IV)=O peaks depicted the dynamic interaction of reactive intermediates along the H2O2 consumption. With this basis, we proposed a mechanism of interfacial OOH* mediated Fe(II) regeneration, which overcame the kinetical limitation of Fe(II)/H2O2 system. Therefore, this study provided a primary effort to elucidate the overlooked role of interfacial CoOOH* in the Fenton-like processes, which may inspire the design of more efficient catalysts.

CCAAT enhancer binding protein delta activates vesicle associated membrane protein 3 transcription to enhance chemoresistance and extracellular PD-L1 expression in triple-negative breast cancer.

BACKGROUND: Chemoresistance and immunosuppression are two major obstacles in the current anti-cancer treatments. This study investigates the involvements of a CCAAT enhancer binding protein delta (CEBPD)/vesicle associated membrane protein 3 (VAMP3) axis in paclitaxel (PTX) resistance and immune evasion in triple-negative breast cancer (TNBC). METHODS: PTX resistance-related genes were screened by bioinformatics. CEBPD and VAMP3 expression in clinical TNBC samples was examined by immunohistochemistry. Three PTX-resistant TNBC cell lines (MDA-MB-231/PTX, MDA-MB-468/PTX and MDA-MB-453/PTX) were generated, and their drug resistance was analyzed. Autophagy of cells was analyzed by immunofluorescence staining. Interaction between CEBPD and VAMP3 promoter was identified by immunoprecipitation and luciferase assays. The extracellular expression of programmed cell death-ligand 1 (PD-L1) in TNBC cells was detected. Extracellular vesicles (EVs) from TNBC cells were isolated to examine their effects on CD8+ T cell exhaustion. RESULTS: CEBPD and VAMP3 were upregulated in chemo-resistant tissue samples and in PTX-resistant TNBC cells. The CEBPD downregulation enhanced PTX sensitivity of cells. However, further upregulation of VAMP3 in cells restored PTX resistance, which was likely due to the activation of autophagy, as the autophagy antagonist chloroquine enhanced PTX sensitivity of cells. CEBPD was found to bind to the VAMP3 promoter to activate its transcription. The CEBPD/VAMP3 axis also increased the PD-L1 expression in the conditioned medium of TNBC cells. The TNBC cell-derived EVs increased the exhaustion of co-cultured CD8+ T cells. CONCLUSION: This study provides novel evidence that CEBPD plays a key role in enhancing PTX resistance in TNBC cells across various subtypes through VAMP3-mediated autophagy activation. Additionally, the CEBPD/VAMP3 axis also increases extracellular PD-L1 level, delivered by cancer cell-derived EVs, to suppress CD8+ T cell-mediated anti-tumor immune response. These significant observations may provide new insights into the treatment of TNBC, suggesting CEBPD and VAMP3 as promising targets to overcome treatment resistance.

Differences in physicochemical properties of pectin extracted from pomelo peel with different extraction techniques.

In order to obtain high yield pomelo peel pectin with better physicochemical properties, four pectin extraction methods, including hot acid extraction (HAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction, and enzymatic assisted extraction (EAE) were compared. MAE led to the highest pectin yield (20.43%), and the lowest pectin recovery was found for EAE (11.94%). The physicochemical properties of pomelo peel pectin obtained by different methods were also significantly different. Pectin samples obtained by MAE had the highest methoxyl content (8.35%), galacturonic acid content (71.36%), and showed a higher apparent viscosity, thermal and emulsion stability. The pectin extracted by EAE showed the highest total phenolic content (12.86%) and lowest particle size (843.69 nm), showing higher DPPH and ABTS scavenging activities than other extract methods. The pectin extracted by HAE had the highest particle size (966.12 nm) and degree of esterification (55.67%). However, Fourier-transform infrared spectroscopy showed that no significant difference occurred among the different methods in the chemical structure of the extracted pectin. This study provides a theoretical basis for the industrial production of pomelo peel pectin.

The influence of hot isostatic pressing on precipitates, mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (wt.%) alloy manufactured by sand casting.

Microstructures and mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (GZ1208K, wt.%) alloy under different treatments (as-cast: signed as nonHIP-GZ1208K, hot isostatic pressing (HIP): signed as HIP-GZ1208K) were characterized. Based on microstructure characterization, two prismatic precipitates, ß' and ß1 precipitates, and one basal precipitate, γ' precipitate, formed in both of nonHIP-GZ1208K and HIP-GZ1208K alloy. According to analysis, the area number density and the size of ß' precipitate could be adjusted through HIP treatment. The area number density of ß' precipitate increased after HIP treatment when aged at 32 h, and the size of ß' precipitate refined in both of the HIP-GZ1208K alloy aged at 8 h and 32 h. Except the influence of HIP treatment on microstructures, the ultimate tensile strength (UTS) and elongation of nonHIP-GZ1208K alloy also improved after HIP treatment. The UTS of the GZ1208K alloy aged at 8 h increased from 348 MPa (nonHIP-) to 371 MPa (HIP-) and the elongation increased from 2.6% to 4.7%. The density of the nonHIP-GZ1208K alloy increased after HIP treatment, that is to say the casting defects could be eliminated and the compactness of microstructures could be increased under the high pressure of HIP treatment.

Tandem Acidic CO2 Electrolysis Coupled with Syngas Fermentation: A Two-Stage Process for Producing Medium-Chain Fatty Acids.

The tandem application of CO2 electrolysis with syngas fermentation holds promise for achieving heightened production rates and improved product quality. However, the significant impact of syngas composition on mixed culture-based microbial chain elongation remains unclear. Additionally, effective methods for generating syngas with an adjustable composition from acidic CO2 electrolysis are currently lacking. This study successfully demonstrated the production of medium-chain fatty acids from CO2 through tandem acidic electrolysis with syngas fermentation. CO could serve as the sole energy source or as the electron donor (when cofed with acetate) for caproate generation. Furthermore, the results of gas diffusion electrode structure engineering highlighted that the use of carbon black, either alone or in combination with graphite, enabled consistent syngas generation with an adjustable composition from acidic CO2 electrolysis (pH 1). The carbon black layer significantly improved the CO selectivity, increasing from 0% to 43.5% (0.05 M K+) and further to 92.4% (0.5 M K+). This enhancement in performance was attributed to the promotion of K+ accumulation, stabilizing catalytically active sites, rather than creating a localized alkaline environment for CO2-to-CO conversion. This research contributes to the advancement of hybrid technology for sustainable CO2 reduction and chemical production.

Effect of Calcium Supplementation and TMEM16A Inhibition on Endoplasmic Reticulum Stress Induced by Dental Fluorosis in Mice.

BACKGROUND: Dental fluorosis is a discoloration of the teeth caused by the excessive consumption of fluoride. It represents a distinct manifestation of chronic fluorosis in dental tissues, exerting adverse effects on the human body, particularly on teeth. The transmembrane protein 16a (TMEM16A) is expressed at the junction of the endoplasmic reticulum and the plasma membrane. Alterations in its channel activity can disrupt endoplasmic reticulum calcium homeostasis and intracellular calcium ion concentration, thereby inducing endoplasmic reticulum stress (ERS). This study aims to investigate the influence of calcium supplements and TMEM16A on ERS in dental fluorosis. METHODS: C57BL/6 mice exhibiting dental fluorosis were subjected to an eight-week treatment with varying calcium concentrations: low (0.071%), medium (0.79%), and high (6.61%). Various assays, including Hematoxylin and Eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (qPCR), and Western blot, were employed to assess the impact of calcium supplements on fluoride content, ameloblast morphology, TMEM16A expression, and endoplasmic reticulum stress-related proteins (calreticulin (CRT), glucose-regulated protein 78 (GRP78), inositol requiring kinase 1α (IRE1α), PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6)) in the incisors of mice affected by dental fluorosis. Furthermore, mice with dental fluorosis were treated with the TMEM16A inhibitor T16Ainh-A01 along with a medium-dose calcium to investigate the influence of TMEM16A on fluoride content, ameloblast morphology, and endoplasmic reticulum stress-related proteins in the context of mouse incisor fluorosis. RESULTS: In comparison to the model mice, the fluoride content in incisors significantly decreased following calcium supplements (p < 0.01). Moreover, the expression of TMEM16A, CRT, GRP78, IRE1α, PERK, and ATF6 were also exhibited a substantial reduction (p < 0.01), with the most pronounced effect observed in the medium-dose calcium group. Additionally, the fluoride content (p < 0.05) and the expression of CRT, GRP78, IRE1α, PERK, and ATF6 (p < 0.01) were further diminished following concurrent treatment with the TMEM16A inhibitor T16Ainh-A01 and a medium dose of calcium. CONCLUSIONS: The supplementation of calcium or the inhibition of TMEM16A expression appears to mitigate the detrimental effects of fluorosis by suppressing endoplasmic reticulum stress. These findings hold implications for identifying potential therapeutic targets in addressing dental fluorosis.

Association of preoperative frailty with the risk of postoperative delirium in older patients undergoing hip fracture surgery: a prospective cohort study.

OBJECTIVE: This study aimed to explore the correlation between preoperative frailty and the risk of postoperative delirium (POD) in older patients undergoing hip fracture surgery. METHODS: In total, 148 patients with hip fractures who were admitted to Tsinghua Changgung Hospital (Beijing, China) between January 2022 and January 2023 were involved in this study. Preoperative frailty scales were assessed, of which the CAM scale was postoperatively administered every morning and evening on days 1, 2, 3, 5, and 7. Binary logistic regression analysis was conducted to determine the correlation between preoperative frailty and the risk of POD. RESULTS: Among 148 older patients with hip fractures, 71 (48.0%) were identified as preoperative frail and 77 (52.0%) as non-frail. The overall incidence of POD on day 7 was 24.3% (36/148), and preoperative frailty was associated with a significantly higher risk of POD compared with non-frailty (42.3% vs. 7.8%, P < 0.001). The binary logistic regression analysis revealed that preoperative frailty was noted as an independent risk factor for the risk of POD in older patients undergoing hip fracture surgery (P = 0.002). CONCLUSION: Preoperative frailty increased the risk of POD in older patients undergoing hip fracture surgery. DISCUSSION: Preoperative assessment of frailty in geriatric hip surgery can timely identify potential risks and provide interventions targeting frailty factors to reduce the incidence of POD in older patients undergoing hip fracture surgery. The findings suggested that preoperative frailty could increase the risk of POD in older patients undergoing hip fracture surgery. Further research is necessary to determine whether perioperative interventions aimed at enhancing frailty can mitigate the risk of POD and improve prognosis in older patients undergoing hip fracture surgery.

Single-cell RNA sequencing reveals association of aberrant placental trophoblasts and FN1 reduction in late-onset fetal growth restriction.

INTRODUCTION: Fetal growth restriction (FGR) can lead to fetal mental development abnormalities, malformations, and even intrauterine death. Defects in the trophoblasts at the maternal-fetal interface may contribute to FGR. However, the impact of trophoblasts on FGR is still not well understood. Therefore, the objective of this study is to characterize the heterogeneity of placental cells at the single-cell level and investigate the role of trophoblast subtypes in the pathogenesis of FGR at the cellular and molecular levels. METHODS: Single-cell RNA sequencing was performed on the maternal side of placentas from two normal pregnant women and two pregnant women with FGR. Lentivirus transfection was used to establish a FN1 knockout model in trophoblast HTR-8-Svneo cells. The effect of FN1 knockout on cell migration and invasion of HTR-8-Svneo cells was assessed through wound healing and transwell assays. RESULTS: Nine cell types were annotated in 39,161 cells derived from single-cell RNA sequencing. The FGR group exhibited a decrease in the percentage of trophoblasts, especially in subtype of extravillous trophoblasts (EVTs). The expression of FN1 was reduced in trophoblasts and EVTs. Furthermore, the protein expression levels of FN1 in the placentas of FGR patients were significantly lower than those of normal pregnant women. The cell migration and invasion ability of HTR-8-Svneo cells were inhibited after the knockdown of FN1. DISCUSSION: The dysregulation of the trophoblast subtype-EVTs is involved in placental dysplasia related to FGR. The association between aberrant placental trophoblasts and reduced FN1 expression may contribute to insufficient remodeling of spiral arteries and the formation of FGR.

Effects of Lactobacillus plantarum FM 17 fermentation on jackfruit polysaccharides: Physicochemical, structural, and bioactive properties.

Fermentation is a novel technology for modifying polysaccharides in fruits and improving their bioactivities. In this work, we introduced Lactobacillus plantarum FM 17 to ferment jackfruit pulp and subsequently purified polysaccharides from unfermented (JP) and fermented jackfruit pulp (JP-F). Furthermore, the physicochemical, structural, and bioactive properties of JP and JP-F were investigated. Results showed fermentation dropped the glucuronic acid, molecular weight, and particle size of JP-F by 15.62 %, 23.92 %, and 39.43 %, respectively, compared with those of JP. JP-F showed higher solubility than JP but lower apparent viscosity and thermal stability. Additionally, FT-IR spectra and X-ray diffraction analysis showed that fermentation did not alter the different types of glycosidic bonds and the fundamental polysaccharide structure. Moreover, JP-F exhibited stronger DPPH and ABTS free radical scavenging properties than JP and stronger stimulation on macrophage secretion of NO and IL-6 in RAW 264.7 cells. Therefore, using L. plantarum FM 17 for fermentation can alter physical and chemical properties of jackfruit pulp polysaccharides, enhancing their bioactivities.

Acute thrombus formation on the delivery sheath during left atrial appendage occlusion: Case reports with placement of cerebral protection devices.

Acute thrombus formation on the delivery sheath is rare condition during percutaneous left atrial appendage occlusion. We presented two cases that transesophageal echocardiography (TEE) showed a floating thrombus attached to the tip of delivery sheath during the procedure. Cerebral embolic protection devices were used to prevent neurological events after thrombus was detected. The neurological function was not impaired post-procedure.

The Effects of Probiotic Lactobacillus rhamnosus GG on Fecal Flora and Serum Markers of Renal Injury in Mice with Chronic Kidney Disease.

BACKGROUND: In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. METHODS: We surgically induced chronic kidney disease in C57BL/6J male mice aged 8-9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. RESULTS: Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein-interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.

Boosted C-C coupling with Cu-Ag alloy sub-nanoclusters for CO2-to-C2H4 photosynthesis.

The selective photocatalytic conversion of CO2 and H2O to high value-added C2H4 remains a great challenge, mainly attributed to the difficulties in C-C coupling of reaction intermediates and desorption of C2H4* intermediates from the catalyst surface. These two key issues can be simultaneously overcome by alloying Ag with Cu which gives enhanced activity to both reactions. Herein, we developed a facile stepwise photodeposition strategy to load Cu-Ag alloy sub-nanoclusters (ASNCs) on TiO2 for CO2 photoreduction to produce C2H4. The optimized catalyst exhibits a record-high C2H4 formation rate (1110.6 ± 82.5 µmol g-1 h-1) with selectivity of 49.1 ± 1.9%, which is an order-of-magnitude enhancement relative to current work for C2H4 photosynthesis. The in situ FT-IR spectra combined with DFT calculations reveal the synergistic effect of Cu and Ag in Cu-Ag ASNCs, which enable an excellent C-C coupling capability like Ag and promoted C2H4* desorption property like Cu, thus advancing the selective and efficient production of C2H4. The present work provides a deeper understanding on cluster chemistry and C-C coupling mechanism for CO2 reduction on ASNCs and develops a feasible strategy for photoreduction CO2 to C2 fuels or industrial feedstocks.

High mobility group box-1: a potential therapeutic target for allergic rhinitis.

Allergic rhinitis (AR) is a prevalent chronic inflammatory disease of the nasal mucosa primarily characterized by symptoms, such as nasal itching, sneezing, runny nose, and nasal congestion. It has a high recurrence rate and low cure rate, with a lack of effective drugs for treatment. The current approach to management focuses on symptom control. High mobility group box-1 (HMGB1) is a highly conserved non-histone protein widely present in the nucleus of eukaryotes. It is recognized as a proinflammatory agent, and recent studies have demonstrated its close association with AR. Here, we will elaborate the role and mechanism of HMGB1 in AR, so as to reveal the potential value of HMGB1 in the occurrence and development of AR, and provide a new target for clinical research on the treatment of AR.

National survey results on effect of COVID-19 pandemic on female surgeons: A new normal work environment.

BACKGROUND: The impact of COVID-19 reaches the overall well-being of women surgeons. We aimed to describe the impact of transitioning to a new challenging environment. METHODS: A survey of 60 quantitative questions using a Likert-like scale was distributed electronically via email across 1200 members of the Association of Women Surgeons in 2021. Family lifestyle factors including care for children, elderly family members, extent of household chores, and impact of COVID-19 pandemic were queried. RESULTS: A total of 139 members responded. Fifty one percent of these respondents had children at home and 31.2% indicated they needed additional help at home during that time. Eighteen percent of those in practice cared for their elderly family members. Of the survey participants, 71.2% felt the COVID pandemic resulted in a worsened clinical practice, with 30.9% noting a decrease in income. CONCLUSIONS: Women surgeons faced crucial challenges during and post pandemic. An awareness of the changing needs of women surgeons is essential.

Spatial Reconstruction of Oligo and Single Cells by De Novo Coalescent Embedding of Transcriptomic Networks.

Single cell RNA-seq (scRNA-seq) profiles conceal temporal and spatial tissue developmental information. De novo reconstruction of single cell temporal trajectory has been fairly addressed, but reverse engineering single cell 3D spatial tissue organization is hitherto landmark based, and de novo spatial reconstruction is a compelling computational open problem. Here it is shown that a proposed algorithm for de novo coalescent embedding (D-CE) of oligo/single cell transcriptomic networks can help to address this problem. Relying on the spatial information encoded in the expression patterns of genes, it is found that D-CE of cell-cell association transcriptomic networks, by preserving mesoscale network organization, captures spatial domains, identifies spatially expressed genes, reconstructs cell samples' 3D spatial distribution, and uncovers spatial domains and markers necessary for understanding the design principles on spatial organization and pattern formation. Comparison to the novoSpaRC and CSOmap (the only available de novo 3D spatial reconstruction methods) on 14 datasets and 497 reconstructions, reveals a significantly superior performance of D-CE.