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Abstract Coenzyme Q10 (CoQ10) is the most consumed dietary supplement and mainly biosynthesized by aerobic fermentation of Rhodobacter sphaeroides (R. sphaeroides). Oxygen supply was identified as a bottleneck for improving CoQ10 yield in R. sphaeroides. In this study, a precise regulation strategy based on dielectric spectroscopy (DS) was applied to further improve CoQ10 biosynthesis by R. sphaeroide. First, a quantitative response model among viable cells, cell morphology, and oxygen uptake rate (OUR) was established. DS could be used to detect viable R. sphaeroides cells, and the relationship among cell morphology, CoQ10 biosynthesis, and OUR was found to be significant. Based on this model, the online specific oxygen consumption rate (QO2) control strategy was successfully applied to the CoQ10 fermentation process. QO2 controlled at 0.07 ± 0.01 × 10− 7mmol/cell/h was most favorable for CoQ10 biosynthesis, resulting in a 28.3% increase in CoQ10 production. Based on the multi-parameters analysis and online QO2 control, a precise online nutrient feeding strategy was established using conductivity detected by DS. CoQ10 production was improved by 35%, reaching 3384 mg/L in 50 L bioreactors. This online control strategy would be effectively applied for improving industrial CoQ10 production, and the precise fermentation control strategy could also be applied to other fermentation process.

Abstract Background Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. Methods This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). Conclusions DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Abstract Purpose The purpose of this study was to compare the learning in the implant dentistry hands-on course to that of the flipped classroom (FC) and the traditional lecture cohorts (control). Materials and methods In this study,80 students were enrolled for the first time in an implant dentistry program. Subsequently, they were divided into two groups. The first, the FC group, which had free access to a video with a PowerPoint presentation on the Chaoxing-WHU-MOOC platform about the implant placement on first molar sites before class. The second, the control group, which attended a didactic lecture describing implant practice on the first molar site via a bidirectional multimedia interactive teaching demonstration and then operated on a simulation model. Cone beam computed tomography (CBCT) and the deviation gauge were utilized to analyze the accuracy of the implant placement in the students’ models. An online satisfaction questionnaire was distributed to both groups one week after the class. Results The linear deviation of the CBCT examination did not show any statistical difference between the two groups concerning cervical, apex, and angular. A significant buccal deviation was observed in the control group compared with the FC group (mean: 0.7436 mm vs. 0.2875 mm, p = 0.0035), according to the restoration-level deviation gauge. A total of 74.36% of students in the FC group placed implant within 0.5 mm buccal-to-lingual deviations, but only 41.03% of students in the control group reached within 0.5 mm buccal-to-lingual deviation ranges. Additionally, 91.67% of the students in the FC group and 97.5% of the students in the control group were satisfied with the practical implant class. Conclusion FC was more effective than a didactic lecture for implant dentistry practical skill acquisition.

Abstract Background The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. Materials and methods This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. Results The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. Conclusion HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.

Abstract Background Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)was reported in some studies, while the diagnosis of TdT (terminal deoxynucleotydil transferase) positive high grade B cell lymphoma (HGBL) with MYC and BCL2 rearrangements (“double hit”) transformed from FL/DLBCL has been rarely reported. Herein, we described the clinical features and mutation profiles of a case diagnosed with TdT positive “double hit” HGBL following the treatment of FL/DLBCL. Case presentation This is a 43-year-old Chinese man who was diagnosed with low grade FL (account for 80%) combined with DLBCL (20%) at a stage of IVB. The patient presented with BCL2/IGH translocation without MYC rearrangement, as well as the expressions of CD20, CD19, CD10 and BCL2 at the initial diagnosis of FL/DLBCL. MYC rearrangement and TdT expression occurred after the treatment. The targeted sequencing revealed mutations in KMT2D, FOXO1, CREBBP, ATM, STAT6, BCL7A, DDX3X, MUC4, FGFR3, ARID5B, DDX11 and PRKCSH genes were the co-mutations shared by the FL/DLBCL and TdT positive “double hit” HGBL, while CCND3, BIRC6, ROBO1 and CHEK2 mutations specifically occurred after the treatment. The overall survival time was 37.8 and 17.8 months after the initial diagnosis of FL/DLBCL and TdT positive “double hit” HGBL, respectively. Conclusion This study reports a rare case of TdT positive “double hit” HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive “double hit” HGBL transformed from FL/DLBCL.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a poor prognosis. Mono-immunotherapy, such as blockade of the PD-1/PD-L1 pathway, for PDAC has proven to be less effective. The systemic exertion of 4–1BB signaling enhanced antitumor immunity accompanied by hepatotoxicity, which is an obstacle for its clinical application. Our study exploits an oncolytic virus armed with 4–1BBL (VV-ΔTK-4L) to locally express 4–1BBL in the tumor microenvironment (TME), thus avoiding hepatotoxicity. VV-ΔTK-4L prolonged the survival time of a pancreatic tumor mouse model and modified the immune status of the TME and spleen. In the TME, the quantities of CD45+ cells, NK1.1+ cells, CD11c+ DCs, CD3+ T, CD4+ T, and CD8+ T cells increased. Compared to VV-ΔTK treatment, VV-ΔTK-4L further increases the number of CD8+ T cells with effector phenotypes, and downregulates exhaustion-related molecules on CD8+ T cells, and does not increase the proportion of Foxp3+ T cells. Thus, the TME of pancreatic cancer was converted from “cold” to “hot” by VV-ΔTK-4L. Blockade of the PD-1/PD-L1 pathway combined with VV-ΔTK-4L further significantly improves the survival ratio of a tumor-bearing mouse model. This study provides a systemic therapeutic strategy and approach for PDAC immunotherapy.

Background Previous research has strongly supported the utility of spaced learning in enhancing memory, but its effectiveness in complex surgical procedures has largely been unexplored. The main objective of this study was to evaluate whether, in comparison to concentrated learning, spaced learning improves the short-term acquisition and long-term retention of cosmetic suturing skills as outcomes of surgical resident training courses.Methods This randomized controlled trial was conducted from February 2023 to June 2023. Surgical residents were recruited from a teaching hospital in Guangzhou, China. The participants were randomly assigned at a 1:1 ratio to either the spaced training group (40 min of training followed by a 20-minute break) or the concentrated training group (3 h of continuous training), in which they received one-on-one training for cosmetic suturing skills. The short-term acquisition and long-term retention outcomes were evaluated by three independent raters using an objective scoring scale to assess the participants’ cosmetic suturing skills before the training (pretraining test), within one hour after the training (posttraining test), and three months after the completion of the training (follow-up test). The score for each participant was calculated as the average of three independent scores.Results The study included 23 surgical residents, 12 in the spaced training group and 11 in the concentrated training group. The pretraining test revealed no significant difference between the groups. However, in the post-training test, the spaced training group achieved a significantly higher total score than did the concentrated training group (74.06 ± 5.87 vs. 63.43 ± 10.73, p = 0.0070). Specifically, the suture technique scores were 28.46 ± 1.78 and 22.85 ± 3.75, respectively, which were significantly different (p = 0.0002). During the long-term follow-up test, the spaced training group consistently outperformed the concentrated training group by having significantly higher total (75.60 ± 4.78 vs. 60.68 ± 10.40, p = 0.0001), suture quality (32.26 ± 4.01 vs. 26.23 ± 4.16, p = 0.0019), suture technique (28.68 ± 2.63 vs. 22.18 ± 3.94, p = 0.0001), and suturing time scores (14.67 ± 1.15 vs. 12.27 ± 6.07, p = 0.0460).Conclusions Incorporating the principles of spaced learning into the instructional process of obtaining cosmetic suture skills for surgical residents not only significantly enhances short-term skill improvement but also contributes to the long-term retention of training outcomes.

Membranous nephropathy (MN) continues to be a leading cause of nephrotic syndrome in non-diabetic adults. As a unique subtype in the serology-based classification of MN, thrombospondin type 1 domain containing 7A (THSD7A)-associated MN has attracted increasing interest, because, unlike other autoantigens, THSD7A is also expressed in preclinical species, facilitating the study of its role in MN. A heterologous mouse model of THSD7A-associated MN was previously established using a proprietary in-house antibody that was unfortunately not available to the research community. Here, we developed a mouse model of THSD7A-associated MN by administering a commercially available antibody targeting the most N-terminal part of THSD7A. Our model was characterized by heavy proteinuria and pathological features of human MN without sex differences. Complement depletion with cobra venom factor only partially attenuated proteinuria and glomerular injury in this model, entailing that complement-independent pathomechanisms also contribute. Consistently, in vitro in primary podocytes, exposure to the anti-THSD7A antibody caused evident podocytopathic changes, including disruption of actin cytoskeleton integrity, podocyte hypermobility, oxidative stress, and apoptotic cell death. These signs of podocytopathy were preserved, albeit to a lesser extent, after complement inactivation, indicating autonomous podocyte injury. Furthermore, as the first FDA-approved treatment for primary MN, adrenocorticotropic hormone therapy with repository corticotropin injection (Purified Cortrophin Gel®) appeared to be beneficial and significantly attenuated proteinuria and glomerular injury, suggesting that this model may be useful for developing novel treatments or understanding the pathogenesis of MN. Collectively, our model, based on the use of a commercially available anti-THSD7A antibody, will be an important tool for MN research.

Abstract Plant chloroplasts have a highly compartmentalized interior, essential for executing photocatalytic functions. However, the construction of a photocatalytic reaction compartment similar to chloroplasts in inorganic–biological hybrid systems (IBS) has not been reported. Drawing inspiration from the compartmentalized chloroplast and the phenomenon of liquid–liquid phase separation, herein, a new strategy is first developed for constructing a photocatalytic subcellular hybrid system through liquid–liquid phase separation technology in living cells. Photosensitizers and in vivo expressed hydrogenases are designed to coassemble within the cell to create subcellular compartments for synergetic photocatalysis. This compartmentalization facilitates efficient electron transfer and light energy utilization, resulting in highly effective H2 production. The subcellular compartments hybrid system (HM/IBSCS) exhibits a nearly 87‐fold increase in H2 production compared to the bare bacteria/hybrid system. Furthermore, the intracellular compartments of the photocatalytic reactor enhance the system's stability obviously, with the bacteria maintaining approximately 81% of their H2 production activity even after undergoing five cycles of photocatalytic hydrogen production. The research brings forward visionary prospects for the field of semi‐artificial photosynthesis, offering new possibilities for advancements in areas such as renewable energy, biomanufacturing, and genetic engineering.

ABSTRACT Drug efflux systems have recently been recognized as a significant mechanism responsible for multidrug resistance in bacteria. In this study, we described the identification and characterization of a new chromosomally encoded efflux pump (SA00565) in Staphylococcus aureus. SA00565, which belongs to the drug/metabolite transporter (DMT) superfamily, was predicted to be a 10-transmembrane segment transporter. To evaluate the role of sa00565 in resistance, we generated sa00565 gene deletion mutant (Δsa00565) and assessed its susceptibility to 35 different antibiotic treatments. Our results demonstrated that the Δsa00565 mutant exhibited reduced resistance to tetracycline and doxycycline, with 64-fold and 12-fold decreased MICs, respectively. The mechanism of SA00565-mediated tetracycline resistance was demonstrated that SA00565 possesses the capability to efficiently extrud intracellular tetracycline into the environment. The efflux activity of SA00565 was further validated using EtBr accumulation and efflux assays. In summary, our study uncovered a previously unknown function of a DMT family transporter, which serves as a tetracycline efflux pump, thereby contributing to tetracycline resistance in S. aureus.IMPORTANCEIn this study, we addressed the significance of drug efflux systems in multidrug resistance of Staphylococcus aureus, focusing on the unexplored efflux pump SA00565 in the drug/metabolite transporter (DMT) superfamily. Through phylogenetic analysis, gene knockout, and overexpression experiments, we identified the role of SA00565 in antibiotic resistance. The Δsa00565 mutant showed increased susceptibility to tetracycline and doxycycline in disk diffusion assays, with significantly lower MICs compared to the WT. Remarkably, intracellular tetracycline concentration in the mutant was two- to threefold higher, indicating SA00565 actively eliminates intracellular tetracycline. Our findings emphasize the pivotal contribution of SA00565 to tetracycline antibiotic resistance in S. aureus, shedding light on its functional attributes within the DMT superfamily and providing valuable insights for combating multidrug resistance.

Emerging evidence suggests that GSK3β, a redox-sensitive transducer downstream of insulin signaling, acts as a convergent point for myriad pathways implicated in kidney injury, repair, and regeneration. However, its role in diabetic kidney disease remains controversial. In cultured glomerular podocytes, exposure to a milieu of type 2 diabetes elicited prominent signs of podocyte injury and degeneration, marked by loss of homeostatic marker proteins like synaptopodin, actin cytoskeleton disruption, oxidative stress, apoptosis, and stress-induced premature senescence, as shown by increased staining for senescence-associated β-galactosidase activity, amplified formation of γH2AX foci, and elevated expression of mediators of senescence signaling, like p21 and p16INK4A. These degenerative changes coincided with GSK3β hyperactivity, as evidenced by GSK3β overexpression and reduced inhibitory phosphorylation of GSK3β, and were averted by tideglusib, a highly-selective small molecule inhibitor of GSK3β. In agreement, post-hoc analysis of a publicly-available glomerular transcriptomics dataset from patients with type 2 diabetic nephropathy revealed that the curated diabetic nephropathy-related gene set was enriched in high GSK3β expression group. Mechanistically, GSK3β-modulated nuclear factor Nrf2 signaling is involved in diabetic podocytopathy, because GSK3β knockdown reinforced Nrf2 antioxidant response and suppressed oxidative stress, resulting in an improvement in podocyte injury and senescence. Conversely, ectopic expression of the constitutively active mutant of GSK3β impaired Nrf2 antioxidant response and augmented oxidative stress, culminating in an exacerbated diabetic podocyte injury and senescence. Moreover, IRS-1 was found to be a cognate substrate of GSK3β for phosphorylation at IRS-1S332, which negatively regulates IRS-1 activity. GSK3β hyperactivity promoted IRS-1 phosphorylation, denoting a desensitized insulin signaling. Consistently, in vivo in db/db mice with diabetic nephropathy, GSK3β was hyperactive in glomerular podocytes, associated with IRS-1 hyperphosphorylation, impaired Nrf2 response and premature senescence. Our finding suggests that GSK3β is likely a novel therapeutic target for treating type 2 diabetic glomerular injury.

Abstract Background The utilization of fructose as a carbon source and energy provider plays a crucial role in bacterial metabolism. Additionally, fructose metabolism directly impacts the pathogenicity and virulence of certain pathogenic microorganisms. Results In this study, we report the discovery of a fructose phosphotransferase system (PTS) in S. aureus. This system comprises three genes, namely fruR, fruK, and fruT, which are co-located in an operon that is indispensable for fructose utilization in S. aureus. Our findings confirm that these three genes are transcribed from a single promoter located upstream of the fruRKT operon. The fruR gene encodes a DeoR-type transcriptional regulator, designated as FruR, which represses the expression of the fruRKT operon by direct binding to its promoter region. Significantly, our experimental data demonstrate that the fruRKT operon can be induced by fructose, suggesting a potential regulatory mechanism involving intracellular fructose-1-phosphate as a direct inducer. Furthermore, we conducted RNA-seq analysis to investigate the specificity of FruR regulation in S. aureus, revealing that the fruRKT operon is predominantly regulated by FruR. Conclusions In summary, this study has uncovered a fructose phosphotransferase system (PTS) in S. aureus, highlighting the essential role of the fruR, fruK, and fruT genes in fructose utilization. We confirmed their co-location within an operon and established FruR as a key regulator by binding to the operon’s promoter. Importantly, we demonstrated that fructose can induce this operon, possibly through intracellular fructose-1-phosphate. Our identification of this PTS system represents the initial characterization of a fructose metabolism system in S. aureus.

The metabolite and flavor characteristics of roasted germinated sunflower seeds (RGSF) were evaluated and compared with those of roasted ungerminated sunflower seeds (RUSF) by gas chromatograph-flame ionization detector (GC-FID) and headspace solid phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS). During roasting, α-tocopherol, β-sitosterol, fructose, and glucose content were higher at 125 °C compared to those at 135 and 145 °C in RGSF, and lower reductions of alanine, glycine, phenylalanine, serine, asparagine, and γ-aminobutyric acid (GABA) content at 125 °C in RGSF. Considering their nutritional value, it is suggested that sunflower seeds are roasted at 125 °C. The dominant volatile compounds in RGSF were α-pinene, furfural, pyrazines, 1-octen-3-ol, and 2-methylbutanal. High-temperature heating for long term led to a large accumulation of unpleasant odors like pyridine, hexanal and nonanal, especially in RUSF. To examine the distribution of the individual metabolites and flavor compounds among different roasting conditions. A heatmap diagram combined with agglomerative hierarchical clustering (AHC) analysis and principal component analysis (PCA) showed that most Maillard reaction substitutes (amino acids and reducing sugars), products (2-methylpyrazine 2-ethyl-3,5-dimethyl-pyrazine, and 3-ethyl-2,5-dimethylpyrazine), and Strecker degradation products (3-methylbutanal, 2-methylbutanal, and isobutanal) contributed to separate RGSF from RUSF.

With the rapid development of medical technology, human dying process has been technicalized and medicalized, but the pain caused by ageing and terminal disease remains widespread. However, Palliative care can alleviate this kind of pain and improve the quality of life for end-stage patients.Over the years, China has introduced a series of policies and laws to include hospice care in the national health system from the legislative level, most healthcare providers, however, are incompetent and unable to understand and deliver palliative care, resulting in the poor quality of death in China. Integration of palliative care into the health system needs to be gradually implemented, by unifying definitions and principles, advocating palliative care practice in clinical work, initiating education in medical students, developing palliative care networks in primary healthcare system, formulating national-level development indicators, and emphasizing localized development, with the hope of avoiding futile or inappropriate treatments at the end of life.

Abstract Mammary mucoepidermoid carcinoma (MEC) is a rare entity. The molecular characteristics of breast MEC have not been fully investigated due to its rarity. We performed a retrospective study among 1000 patients with breast carcinomas and identified four cases of breast MEC. Clinical and demographic data were collected. Immunohistochemistry panels which were used to diagnose salivary gland MEC and breast carcinomas were also performed. MAML2 rearrangements were detected by FISH and fusion partners were identified by RNA sequencing. Whole-exome sequencing (WES) was used to reveal the genomes of these four breast MEC. Then, the biological functions and features of breast MEC were further compared with those of invasive breast carcinomas and salivary gland MEC. According to Ellis and Auclair’s methods, these four breast MEC could be classified as low-grade breast MEC. All the patients were alive, and disease-free survival (PFS) ranged from 20 months to 67 months. Among these four breast MEC, two cases were triple-negative, and the other two cases were found to be ER positive, with one also showing HER2 equivocal by immunohistochemical staining, but no amplification in FISH. FISH analysis confirmed the presence of the MAML2 translocation in three of four tumors, and CRTC1-MAML2 fusion was confirmed in two of them by RNA-sequencing. The average coverage size of WES for the tumor mutation burden estimation was 32 Mb. MUC4, RP1L1 and QRICH2 mutations were identified in at least three tumors, and these mutation also existed in breast invasive carcinoma databases (TCGA, Cell 2015; TCGA, Nature 2012). The results showed that there were many genes in breast MEC overlapping with the breast invasive carcinoma databases mentioned above, range from 5 to 63 genes (median:21 genes). Next, we assessed immune cell infiltration levels in these tumors. In all these tumors, M2 macrophages and plasma cell were in the high infiltration group. Our breast MEC showed different results from the salivary gland MEC, whose plasma cells were in the low infiltration group. Overall, we first analyzed the genomics and tumor microenvironment of breast mucoepidermoid carcinoma and proposed our hypothesis that although MECs arising in the breast resemble their salivary gland counterparts phenotypically, our findings indicate that breast MECs probably resemble invasive breast carcinomas at the genetic level and immune cell infiltration levels. More cases and in deep research need to be done to further understand this rare carcinoma.

Abstract Underwater pottery relics salvaged from shipwrecks are vulnerable to physical, chemical and biological corrosion. In this study, the microscopic morphology and structural composition of glazed pottery fragments excavated from the South China Sea as well as purple clay teapot samples from the Yangtze River Estuary II shipwreck were analyzed by means of optical microscopy, scanning electron microscope equipped with energy dispersive spectrometer, X-ray diffraction, X-ray photoelectron spectroscopy, Fourier infrared transform spectroscopy and photoluminescence spectroscopy. According to the research results, the corrosion products deposited on the surface of the glazed pottery fragment from the South China Sea mainly included FeOOH and MnO2, whereas those on the surface of the purple clay teapot fragment from the Yangtze River Estuary II shipwreck primarily incorporated FeS2 and FeS. According to the corrosion phenomenon, it was speculated that the underwater pottery relics were mainly corroded by different microorganisms in the underwater environment, including manganese-oxidizing bacteria, dissimilatory metal-reducing bacteria and sulfate-reducing bacteria. As the corrosion process of these cultural artifacts was described and related models were established, this study provides valuable reference for the disease removal and protection of pottery relics.

Cells constitute the fundamental units of living organisms. Investigating individual differences at the single-cell level facilitates an understanding of cell differentiation, development, gene expression, and cellular characteristics, unveiling the underlying laws governing life activities in depth. In recent years, the integration of single-cell manipulation and recognition technologies into detection and sorting systems has emerged as a powerful tool for advancing single-cell research. Raman cell sorting technology has garnered attention owing to its non-labeling, non-destructive detection features and the capability to analyze samples containing water. In addition, this technology can provide live cells for subsequent genomics analysis and gene sequencing. This paper emphasizes the importance of single-cell research, describes the single-cell research methods that currently exist, including single-cell manipulation and single-cell identification techniques, and highlights the advantages of Raman spectroscopy in the field of single-cell analysis by comparing it with the fluorescence-activated cell sorting (FACS) technique. It describes various existing Raman cell sorting techniques and introduces their respective advantages and disadvantages. The above techniques were compared and analyzed, considering a variety of factors. The current bottlenecks include weak single-cell spontaneous Raman signals and the requirement for a prolonged total cell exposure time, significantly constraining Raman cell sorting technology’s detection speed, efficiency, and throughput. This paper provides an overview of current methods for enhancing weak spontaneous Raman signals and their associated advantages and disadvantages. Finally, the paper outlines the detailed information related to the Raman cell sorting technology mentioned in this paper and discusses the development trends and direction of Raman cell sorting.

Current online transactions of aquatic products are often plagued by problems such as low efficiency, high platform supervision cost, insufficient trust and leakage of transaction data. Blockchain has been widely used in many different fields due to its decentralization, non-tampering and distributed data management. In order to resolve the existing problems, a blockchain-based aquatic product trading matching model integrated with credit mechanisms is proposed in this study to improve the efficiency, quality, security and satisfaction of online transactions for aquatic products. Then, based on this model, an online trading matching prototype system for aquatic products is developed, taking the Hyperledger Fabric as the underlying architecture. The performance testing of the prototype system has demonstrated that the introduction of the credit mechanism has a certain improvement effect on the trading matching results of aquatic products, and the system can complete more than 1000 transactions within half an hour, which can satisfy the normal business-to-business online transaction needs for aquatic products. To a certain extent, it can reduce the security risks and supervision cost, and improve the efficiency and satisfaction of online transaction. This study can also bring insights to blockchain-based online trading models in other industry fields.

Abstract Non-obese diabetic (NOD) mice were taken as primary Sjögren’s syndrome (pSS) model mice to examine the therapeutic impact of iguratimod (IGU) on inflammatory factors levels and apoptosis of submandibular epithelial cells, and provide experimental basis for the treatment of pSS by iguratimod. Twenty-four NOD murine models were divided into the model, high-dose (IGU 30 mg/kg) and low-dose (IGU 10 mg/kg) groups, eight mice per group. The normal control group comprised eight C57B/L mice. From 8 weeks of age, the NOD mice were administered IGU by intragastric gavage administration every day for 8 weeks; their water consumption, saliva secretion, submandibular gland, and spleen indices were measured. The levels of serum inflammatory factor (IL-1β, TNF-α, IL-6, and IL-17) were evaluated, and Bax, caspase-3, and Bcl-2 levels were detected. The histological alterations in the submandibular glands were discovered. IGU can reduce the water intake of NOD mice (p

Abstract A multiomics study was conducted to investigate how lipid metabolism disorders affect the immune system in Xinjiang patients with hyperuricemia. The serum of 60 healthy individuals and 60 patients with hyperuricemia was collected. This study used LC–MS and HPLC to analyze differential lipid metabolites and enrichment pathways. It measured levels of immune factors tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), carnitine palmitoyltransferase-1 (CPT1), transforming growth factor-β1 (TGF-β1), glucose (Glu), lactic acid (LD), interleukin 10 (IL-10), and selenoprotein 1 (SEP1) using ELISA, as well as to confirm dysregulation of lipid metabolism in hyperuricemia. 33 differential lipid metabolites were significantly upregulated in patients with hyperuricemia. These lipid metabolites were involved in arachidonic acid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, glycosylphosphatidylinositol (GPI)—anchor biosynthesis, and alpha-Linolenic acid metabolism pathways. Moreover, IL-10, CPT1, IL-6, SEP1, TGF-β1, Glu, TNF-α, and LD were associated with glycerophospholipid metabolism. In patients with hyperuricemia of Han and Uyghur nationalities, along with healthy individuals, significant differences in CPT1, TGF-β1, Glu, and LD were demonstrated by ELISA (P

In this study, we extend the research on the multimodal routing problem by considering flexible time window and multi-uncertainty environment. A multi-uncertainty environment includes uncertainty regarding the demand for goods, the travel speed of the transportation mode, and the transfer time between different transportation modes. This environment further results in uncertainty regarding the delivery time of goods at their destination and the earliness and lateness caused by time window violations. This study adopts triangular fuzzy numbers to model the uncertain parameters and the resulting uncertain variables. Then, a fuzzy mixed integer nonlinear programming model is established to formulate the specific problem, including both fuzzy parameters and fuzzy variables. To make the problem easily solvable, this study employs chance-constrained programming and linearization to process the proposed model to obtain an equivalent credibilistic chance-constrained linear programming reformulation with an attainable global optimum solution. A numerical case study based on a commonly used multimodal network structure is presented to demonstrate the feasibility of the proposed method. Compared to hard and soft time windows, the numerical case analysis reveals the advantages of the flexible time window in reducing the total costs, avoiding low reliability regarding timeliness, and providing confidence level-sensitive route schemes to achieve flexible routing decision-making under uncertainty. Furthermore, the numerical case analysis verifies that it is necessary to model the multi-uncertainty environment to satisfy the improved customer requirements for timeliness and enhance the flexibility of the routing, and multimodal transportation is better than unimodal transportation when routing goods in an uncertain environment. The sensitivity analysis in the numerical case study shows the conflicting relationship between the economic objective and the reliability regarding the timeliness of the routing, and the result provides a reference for the customer to find a balance between them.

Abstract Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein–protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a “drug component–target gene–disease” network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer.

Based on the microdata of 705 wheat farmers in the Loess Plateau, this study empirically analyzes the impact of uncertainty on farmers’ adoption of innovative seeds using a field experiment. The results indicate that farmers are generally ambiguity-averse and risk-averse. In addition, farmers with higher ambiguity aversion and risk aversion are less likely to adopt innovative wheat seeds, where their risk aversion plays a dominant role. Enhancing information access will alleviate the negative influence of ambiguity aversion on farmers’ adoption of innovative seeds, and interlinked insurance and credit contracts will be beneficial to ease the adverse effect of risk aversion on the adoption of innovative wheat seeds. Meanwhile, heterogeneity analysis reveals that the inhibitory effects of ambiguity aversion and risk aversion on innovative seed adoption are more significant among farmers with lower education and household income. The government can establish both ex-ante and ex-post relevant guarantee mechanisms to help farmers preferably cope with various uncertainties in the production process, remitting farmers’ ambiguity aversion and risk aversion to enhance new agricultural technology adoption rates.

Background: Epidemiological evidence suggests that hyperinsulinemia or insulin resistance is a significant risk factor for the development of diabetic complications such as DKD. However, whether hyperinsulinemia per se plays a causative role in the development of diabetic kidney injury is unknown and was explored here. Methods: Pre-diabetic db/db mice were examined for serum insulin levels, urinary albumin to creatinine ratios and renal histology. Conditionally immortalized mouse podocytes were cultured under non-permissive conditions and exposed to high ambient insulin conditions, following GSK3beta silencing, ectopic expression of a constitutively active GSK3beta mutant (S9A), or treatment with a small molecule GSK3beta inhibitor tideglusib. Podocyte injury was assessed and signaling pathways examined. Results: In pre-diabetic db/db mice, hyperinsulinemia was evident and associated with microalbuminuria and early signs of podocyte impairment, including diminished expression of homeostatic marker proteins like synaptopodin, as compared with db/m littermates. In vitro, prolonged exposure of differentiated podocytes to high ambient insulin induced podocytopathic changes, including cellular hypertrophy, loss of synaptopodin, and disruption of actin cytoskeleton integrity. This was associated with a desensitized insulin signaling and diminished inhibitory phosphorylation of GSK3beta, denoting GSK3beta hyperactivity. In pre-diabetic db/db mice, GSK3beta hyperactivity was confirmed in glomerular podocytes, correlating with the level of hyperinsulinemia or microalbuminuria. In cultured podocytes, ectopic expression of S9A caused podocyte hypertrophy and podocytopathic changes, reminiscent of the harmful effect of the hyperinsulinemic milieu. Conversely, GSK3beta knockdown mitigates podocyte injury elicited by hyperinsulinemic milieu. This protective effect was mimicked by the small molecule inhibitor tideglusib. Conclusions: GSK3beta hyperactivity is required and sufficient for Hyperinsulinemic milieu-elicited glomerular podocyte impairment and dysfunction.

This paper presents an automatic optimization system for the heat source layout of multi-chip modules, referred to as IOS. The system aims to optimize the heat source layout of multi-chip modules through the integration of multiple software tools. The IOS utilizes an optimization algorithm, WINDOW DOS, and other methods to achieve this goal. Initially, two optimization strategies are introduced which are utilized in conjunction with the Non-dominated Sorting Genetic Algorithm-II(NSGA-II). Subsequently, a simplified thermal model of the multi-chip module is applied to the IOS. The automatic optimization module is then used to optimize the heat source layout. In the end, we simulated and analyzed the application results. The simulation analysis reveals that when the temperature extreme value index is optimized, the PCB board’s transient temperature range falls within [343.14 K, 344.09 K]. Similarly, when the temperature homogeneity index is optimized, the PCB board’s transient temperature range falls within [343.39 K, 344.21 K]. Comparing these results with the experience layout, the temperature difference is reduced by 76.36% and 79.60%, respectively. The optimization results demonstrate that the IOS has a significant impact, offering remarkable optimization effects, low cost, high efficiency, and a more uniform temperature distribution. These findings indicate that the IOS holds promising potential for applications and provides value in optimizing the heat source layout of multi-chip modules.

Encouraging the use of conservation tillage technology is a highly effective approach to safeguarding soil health, improving the environment, and promoting sustainable agricultural development. With the mounting concerns surrounding climate change, developing conservation tillage methods that facilitate sustainable agricultural growth has become an imperative both in China and around the world. While it is widely recognized that adapting to climate change is crucial in agriculture, there is limited research on evaluating the risks, discovering resilience, measuring farmers’ perceptions on climate change, and exploring how tillage technology can be adjusted in the context of small-scale farming in China to foster sustainable development. Using research data from smallholder farmers in the Shaanxi and Shanxi provinces of China, this paper aims to explore the impact of climate change perceptions on farmers’ adoption of conservation tillage technologies based on an ordered Probit model. We found that farmers tend to refrain from embracing conservation tillage technology due to the presence of unclear and conflicting perceptions regarding climate change. Focus on short-term profitability and inadequate preparation hinder them from prioritizing adaptation. We recognized several measures that could help farmers adapt and thrive within the agricultural sector. Furthermore, we have validated the need for self-system moderation in promoting farmers’ adoption of conservation tillage technology. By utilizing such tools and resources, farmers can comprehend the gravity of climate change’s impact on agricultural productivity and, more importantly, channel their efforts towards fortifying resilience to extreme weather conditions and long-term climate risks, thus fortifying agricultural sustainability.

Objective Little is known about spatial variability of hospitalisation rate (HR) of patients with rheumatoid arthritis (RA) worldwide, especially in China.Methods A cross-sectional study was conducted among patients with RA admitted to hospitals in Hunan Province. Global Moran’s I and local indicators of spatial association were used to explore the geospatial pattern of the HR of patients with RA. Generalised estimating equation analysis and geographically weighted regression were used to identify the potential influencing factors of the HR of patients with RA.Results There were a total of 11 599 admissions, and the average HR was 1.57 per 10 000 population in Hunan. We detected different cluster patterns of the HR among patients with RA by local indicators of spatial association. Age, ethnicity, average temperature, average temperature range, average rainfall, regions, gross domestic product per capita, and doctors and hospitals per 10 000 people were risk factors for the HR. However, only average temperature, gross domestic product per capita and hospitals per 10 000 people showed different regression coefficients on the HR in different counties. The increase in hospitals increased the probability of HR from east to west in Hunan with a positive coefficient, while temperature decreases increased the risk of HR from south to north negatively. Similarly, the growth of gross domestic product per capita decreased the probability of HR from southwest to northeast.Conclusion A non-random spatial distribution of the HR of patients with RA was demonstrated in Hunan, and average temperature, gross domestic product per capita and hospitals per 10 000 people showed different regression coefficients on the HR in different counties. Our study indicated that spatial and geostatistics may be useful approaches for further study among patients with RA.

Species distribution models (SDMs) have been widely used to predict potentially suitable habitats for invasive alien species (IAS) and evaluate invasion risk. However, SDMs have been discredited because they ignore the physiological processes by which species respond to their environment. Integrating physiological tolerance into the model is essential to improve the prediction accuracy of SDMs. Currently, this approach has not been applied in the study of the worldwide invasive species, the red-eared slider (Trachemys scripta elegans), which is one of the world’s 100 worst invasive species and is widespread in China. In this study, based on hatching experiments, we found that the embryo temperature tolerance range of the red-eared slider was between 21.8 °C and 33.1 °C. Further, we studied the effect of embryo temperature tolerance on the prediction of potential invasion areas for this alien reptile species. The high suitability area (530,214.71 km2) predicted by the SDM incorporating embryo temperature tolerance data were 20.9% smaller than that (641,107.60 km2) predicted by the SDM without considering embryo temperature tolerance. The difference between the two SDMs is primarily concentrated at the edges of the high suitability areas. The incorporation of embryo temperature tolerance data influenced the model's predictions by effectively reducing the extent of edges of the high suitability areas. High suitability areas for red-eared sliders are mainly concentrated in South China, Central China, and East China, with a few in North and Southwest China. There is almost no invasion risk in most of the northeast and northwest provinces of China. This study not only has theoretical significance for optimizing model predictions, but also provides an important scientific basis for prevention and risk assessment of invasion by red-eared sliders in China.

Summary: The critically endangered big-headed turtle (Platysternon megacephalum) is currently classified into three subspecies. However, the classification is still controversial and their evolutionary histories are still unclear. Here, multiple genetic analyses consistently revealed three phylogenetic groups with substantial genetic divergences and distinct demographic histories, suggesting three phylogenetic species (P. megacephalum, P. peguense, and Baise clade). Phylogeographical analyses revealed that the Red River plains and Guangxi basins are largely coincident with the boundaries between the three phylogenetic species, highlighting the key role of lowland areas in driving speciation in the big-headed turtle. The Baise clade is characterized by high-linkage disequilibrium but the lowest effective population size, indicating that the cryptic phylogenetic species is more vulnerable to human activities and environmental disturbance, and urgently needs more protection. Our findings provide fundamental insights into the taxonomy and scientific conservation of the family Platysternidae.

Abstract The big‐headed turtle (Platysternon megacephalum) is an endemic chelonian species in Asia. Unlike most other turtles in the world, P. megacephalum is characterized with eagle‐beak jaw, large head, and long tail. Although these unique characteristics are well recognized, the underlying genetic basis remains largely elusive. Here, we performed comparative genomic analysis between P. megacephalum and other representative species, aiming to reveal the genetic basis of the unique morphological features. Our results revealed that the eagle‐beak jaw is most likely enabled by combined effects of expansion of SFRP5, extraction of FGF11, and mutation of both ZFYVE16 and PAX6. Large head is supported by mutations of SETD2 and FGRF2 and copy number variations of six head circumference modulation‐related genes (TGFBR2, Twist2, Rdh10, Gas1, Chst11, and SNAP25). The long tail is probably involved in a genetic network comprising Gdf11, Lin 28, and HoxC12, two of which showed a consistent expression pattern with a model organism (mice). These findings suggest that expansion, extraction, and mutation of those genes may have profound effects on unique phenotypes of P. megacephalum.

The yellow pond turtle (Mauremys mutica) is widely cultured for food, medicine and for keeping as pets in China. The high risk of disease outbreaks and mortality caused by sudden sharp temperature drop events has significant negative effects on the aquaculture industry of M. mutica. However, the mechanism underlying the damage caused by cold stress is still unclear. To fill this gap, we performed transcriptome sequencing of M. mutica samples collected at three sampling time points (3h, 24h and 48h) during cold treatment, and at a recovery time point (96 h after the end of cold stress). The results showed that immunity and metabolism-related pathways (neuroactive ligand-receptor interactions, cytokine-cytokine receptor interactions and NOD-like receptor signaling pathways) were significantly enriched at both 24h and 48h. The expression of immunity and metabolism-related genes (BS2A1, PIWIL2 and Fads1) significantly decreased at all-time points compared to the control group. These results suggested that impaired immunity and depressed metabolism under cold stress may be the main cause of the massive cold-stress mortality of M. mutica. This study provides novel insights into the molecular mechanisms underlying mass disease and mortality caused by sudden sharp temperature drop events in M. mutica.

Abstract Biochar is considered to be a possible means of carbon sequestration to alleviate climate change. However, the dynamics of the microbial community during wood decomposition after biochar application remain poorly understood. In this study, the wood-inhabiting bacterial community composition and its potential functions during a two-year decomposition period after the addition of different amounts of biochar (0.5 kg m−2 and 1.0 kg m−2), and at different biochar pyrolysis temperatures (500 °C and 650 °C), in a boreal Scots pine forest, were analyzed using Illumina NovaSeq sequencing combined with Functional Annotation of Prokaryotic Taxa (FAPROTAX). The results showed that the wood decomposition rates increased after biochar addition to the soil surface in the second year. Treatment with biochar produced at high temperatures increased the diversity of wood-inhabiting bacteria more than that produced at low temperatures (P

Objective To study an effective, safe, painless theraphy which is easy accepted by patients and their parents for pediatric facial vitiligo. Methods A total of 98 cases (269 places) with vitiligo on the face in the dermatology clinics from two hospitals (Zhongshan Hospital of Traditional Chinese Medicine and Shaoguan Dermatology Hospital) were observed from May 2017 to October 2020. Each hospital was an independent unit, numbered and grouped according to the order of visit time. These patients in the control group (131 skin lesions) was treated with excimer laser only twice a week, while those patients in the treatment group (138 skin lesions) was treated with excimer laser and external tacrolimus (twice a day). The efficacy and adverse reactions of the two groups of children were evaluated after 3 months of treatment. Results The total effective rate for patients in the treatment group was 92.03%, and the adverse reaction rate was 6.52%; while the total effective rate for patients in the control group was 79.39%, and the adverse reaction rate was 6.11%. The difference was statistically significant (χ2=8.85, P0.05). Conclusion Tacrolimus combined with 308 nm excimer laser in the treatment of facial vitiligo in children has the advantages of convenient operation, definite curative effect, safe and painless, and easy to be accepted by children and parents.

We firstly propose the integration of heterogeneous Tm:YAG and Ho:YAP crystals into a single bulk structure for a compact, diode-pumped passively Q-switched (PQS) Ho laser. Efficient 2129 nm laser, with maximum CW power of 6.67 W was obtained from the Tm:YAG/Ho:YAP gain medium, with slope efficiency of 38.3% and optical conversion efficiency of 27.4% by considering the incident diode power at 785 nm. Modulated by a Cr:ZnSe saturable absorber inside a hybrid cavity, characteristic self-pulsing of the integrated Ho laser can be suppressed for a stable PQS process, where average output power of 743 mW at 2053.3 nm was obtained with shortest pulse duration of 123 ns at 14.2 kHz. As the maximum thermal stress of 48.2 MPa is far below the fracture limits of each integrated section (∼160 MPa), higher laser power can be expected. The results pave the way to explore the integration of other existing Tm-doped and Ho-doped hosts for an accessible 2.1 μm source.

This mini-review summarizes the seminal exploration of aqueous supramolecular chemistry of crown ether macrocycles. In history, most research of crown ethers were focusing on their supramolecular chemistry in organic phase or in gas phase. In sharp contrast, the recent research evidently reveal that crown ethers are very suitable for studying abroad range of the properties and applications of water interactions, from: high water-solubility, control of Hofmeister series, “structural water”, and supramolecular adhesives. Key studies revealing more details about the properties of water and aqueous solutions are highlighted.

Straw returning technology has the potential to not only enhance the crop’s nitrogen yield but also protect the ecological environment and enhance crop yield. This paper explores the impact of uncertainty on rural households’ adoption of straw returning technology using an experimental method based on 703 wheat planting households in the Loess Plateau, China. The results show that 1) most farmers are inclined to risk aversion, and farmers generally have the characteristics of ambiguity aversion. 2) Risk preference and ambiguity preference obviously and negatively impact the possibility of adopting straw returning technology, and when the farmer’s risk preference and ambiguity preference increase by 0.1 units, the probability of adopting straw returning technology will decrease by 19.4% and 17.1%, respectively. 3) When we take the risk preference and ambiguity preference together into account, risk preference has sufficiently large effects on farmers’ decision on adopting straw returning technology relative to ambiguity preference. Overall, this research provides a micro-foundation and policy recommendations for farmers’ straw returning technology promotion in rural China and sheds light upon how the government can formulate relevant policies to promote green environmental development.

ABSTRACT Tuberculosis (TB) caused by Mycobacterium tuberculosis infection remains one of the most serious global health problems. Fluoroquinolones (FQs) are an important component of drug regimens against multidrug-resistant tuberculosis, but challenged by the emergence of FQ-resistant strains. Mycobacterium fluoroquinolone resistance protein A (MfpA) is a pentapeptide protein that confers resistance to FQs. MfpA is the fifth gene in the mfp operon among most Mycobacterium, implying other mfp genes might regulate the activity of MfpA. To elucidate the function of this operon, we constructed deletion mutants and rescued strains and found that MfpD is a GTPase-activating protein (GAP) involved in FQs activity. We showed that the recombinant strains overexpressing mfpD became more sensitive to FQs, whereas an mfpD deletion mutant was more resistant to FQs. By using site-directed mutagenesis and mycobacterial protein fragment complementation, we genetically demonstrated that mfpD participated in FQs susceptibility via directly acting on mfpB. We further biochemically demonstrated that MfpD was a GAP capable of stimulating the GTPase activity of MfpB. Our studies suggest that MfpD, a GAP of MfpB, is involved in MfpA-mediated FQs resistance. The function of MfpD adds new insights into the role of the mfp operon in Mycobacterium fluoroquinolone resistance. IMPORTANCE Tuberculosis is one of the leading causes of morbidity and mortality worldwide largely due to increasingly prevalent drug-resistant strains. Fluoroquinolones are important antibiotics used for treating multidrug-resistant tuberculosis (MDR-TB). The resistance mechanism mediated by the Mycobacterium fluoroquinolone resistance protein (MfpA) is unique in Mycobacterium. However, the regulatory mechanism of MfpA remains largely unclear. In this study, we first report that MfpD acts as a GAP for MfpB and characterize a novel pathway that controls Mycobacterium small G proteins. Our findings provide new insights into the regulation of MfpA and inspiration for new candidate targets for the discovery and development of anti-TB drugs.

ObjectiveThe relationship between gender and short-term prognosis of patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is unclear, hence single-center retrospective analysis and meta-analysis were conducted to determine the relationship.MethodsInitially treated patients with AAV were retrospectively enrolled. Data of clinical manifestation, laboratory indicators, Birmingham vasculitis activity score (BVAS), therapeutic treatments, and the patients' situations within 1 year were recorded. First, we compared the basic characteristics between male and female patients. Second, the risk factors associated with a 1-year mortality rate of patients with AAV were evaluated. Finally, a meta-analysis was performed to explore the effect of gender on 1-year mortality in patients with AAV.ResultsThe study involved 84 patients with AAV, including 33 female and 51 male participants. In total, 14 people died (12 males and 2 females) and 70 survived in the 1st year. Statistical differences were noted in the age of onset, the course of the disease, WBC, HB, N, ESR, CRP, BUN, ALT and ALB, BVAS, and 1-year mortality rate between male and female participants. In male patients, elevated Scr, NLR, PLT, and RDW-CV were associated with poor AAV (P < 0.05) prognosis. The meta-analysis verified that male gender was an independent risk factor for the 1-year mortality of patients with AAV(OR = 1.54).ConclusionSignificant sex-specific differences were found in patients with AAV. Male patients contributed to 1.54-fold of 1-year mortality risk in patients with AAV by meta-analysis. More attention should be paid to the mortality risk of male patients with AAV in the early stage.

Clinical evidence indicates that the melanocortin peptide ACTH is effective in inducing remission of nephrotic glomerulopathies like minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), including those resistant to steroids. This suggests that a steroid-independent melancortinergic mechanism may contribute. However, the type of melanocortin receptor (MCR) that conveys this beneficial effect as well as the underlying mechanisms remain controversial. Burgeoning evidence suggests that MC5R is expressed in glomeruli and may be involved in glomerular pathobiology. This study aims to test the effectiveness of a novel highly selective MC5R agonist (MC5R-A) in puromycin aminonucleoside (PAN) nephrosis. Upon PAN injury, rats developed evident proteinuria on day 5, denoting an established nephrotic glomerulopathy. Following vehicle treatment, proteinuria continued to persist on day 14 with prominent histologic signs of podocytopathy, marked by ultrastructural glomerular lesions, including extensive podocyte foot process effacement. Concomitantly, there was loss of podocyte homeostatic markers, such as synaptopodin and podocin, and de novo expression of the podocyte injury marker desmin. Treatment with MC5R-A attenuated urine protein excretion and mitigated the loss of podocyte marker proteins, resulting in improved podocyte ultrastructural changes. In vitro in cultured podocytes, MC5R-A prevented the PAN-induced disruption of actin cytoskeleton integrity and apoptosis. MC5R-A treatment in PAN-injured podocytes also reinstated inhibitory phosphorylation and thus averted hyperactivity of GSK3β, a convergent point of multiple podocytopathic pathways. Collectively, pharmacologic activation of MC5R by using the highly selective small-molecule agonist is likely a promising therapeutic strategy to improve proteinuria and glomerular injury in protenuric nephropathies.

Aortoesophageal fistula (AEF) caused by esophageal foreign body (EFB) ingestion is a life-threatening condition with a very low survival rate. However, the optimal management strategy remains undetermined. Here, we describe our successful management of a patient with AEF and mediastinitis. A 36-year-old man developed persistent chest and back pain and vomited fresh blood three days after removal of a pork bone in the esophagus under endoscopy in a local hospital. Computed tomography (CT) confirmed bilateral pulmonary infections, mediastinitis, and fistula of the aortic arch. After a multidiscipline discussion, a comprehensive staged strategy was made including salvaged thoracic endovascular aortic repair (TEVAR) to control fatal bleeding, adequate mediastinal debridement, drainage with cervical incision, and video-assisted thoracoscopic surgery, as well as jejunostomy to prevent nasal or gastrostomy reflux from aggravating the mediastinal infection. Furthermore, systematic personalized nutrition support and antibiotics were provided. The patient recovered well and has survived for 50 months until now. Careful assessment should be made with CT to ascertain the risk of AEF before and after the removal of EFB. A salvaged staged strategy of TEVAR with adequate mediastinal debridement and drainage in a less invasive approach may be a safer alternative for AEF patients with infections caused by EFB.

Abstract Renal tubular epithelial cells (TECs) play a key role in renal fibrogenesis. After persistent injuries that are beyond self-healing capacity, TECs will dedifferentiate, undergo growth arrest, convert to profibrogenic phenotypes, and resort to maladaptive plasticity that ultimately results in renal fibrosis. Evidence suggests that glycogen synthase kinase (GSK) 3β is centrally implicated in kidney injury. However, its role in renal fibrogenesis is obscure. Analysis of publicly available kidney transcriptome database demonstrated that patients with progressive chronic kidney disease (CKD) exhibited GSK3β overexpression in renal tubulointerstitium, in which the predefined hallmark gene sets implicated in fibrogenesis were remarkably enriched. In vitro, TGF-β1 treatment augmented GSK3β expression in TECs, concomitant with dedifferentiation, cell cycle arrest at G2/M phase, excessive accumulation of extracellular matrix, and overproduction of profibrotic cytokines like PAI-1 and CTGF. All these profibrogenic phenotypes were largely abrogated by GSK3β inhibitors or by ectopic expression of a dominant-negative mutant of GSK3β but reinforced in cells expressing the constitutively active mutant of GSK3β. Mechanistically, GSK3β suppressed, whereas inhibiting GSK3β facilitated, the activity of cAMP response element-binding protein (CREB), which competes for CREB-binding protein, a transcriptional coactivator essential for TGF-β1/Smad signaling pathway to drive TECs profibrogenic plasticity. In vivo, in mice with folic acid-induced progressive CKD, targeting of GSK3β in renal tubules via genetic ablation or by microdose lithium mitigated the profibrogenic plasticity of TEC, concomitant with attenuated interstitial fibrosis and tubular atrophy. Collectively, GSK3β is likely a pragmatic therapeutic target for averting profibrogenic plasticity of TECs and improving renal fibrosis.

UBASH3A is a negative regulator of T cell activation and IL-2 production and plays key roles in autoimmunity. Although previous studies revealed the individual effects of UBASH3A on risk for type 1 diabetes (T1D; a common autoimmune disease), the relationship of UBASH3A with other T1D risk factors remains largely unknown. Given that another well-known T1D risk factor, PTPN22, also inhibits T cell activation and IL-2 production, we investigated the relationship between UBASH3A and PTPN22. We found that UBASH3A, via its Src homology 3 (SH3) domain, physically interacts with PTPN22 in T cells, and that this interaction is not altered by the T1D risk coding variant rs2476601 in PTPN22. Furthermore, our analysis of RNA-seq data from T1D cases showed that the amounts of UBASH3A and PTPN22 transcripts exert a cooperative effect on IL2 expression in human primary CD8+ T cells. Finally, our genetic association analyses revealed that two independent T1D risk variants, rs11203203 in UBASH3A and rs2476601 in PTPN22, interact statistically, jointly affecting risk for T1D. In summary, our study reveals novel interactions, both biochemical and statistical, between two independent T1D risk loci, and suggests how these interactions may affect T cell function and increase risk for T1D.

Wood, as a naturally green and environmentally friendly material, has been widely used in the construction and decoration industries. However, the flammability of wood poses serious safety problems. To improve the fire resistance of wood, In this study, it is proposed to use calcium chloride (CaCl2) and disodium hydrogen phosphate (Na2HPO4, DSP) to impregnate wood for multiple cycles. The experimental results show that phosphate mineral precipitation can be deposited on the surface of the wood. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) are used to analyze the micromorphology of mineral precipitation and use the MIP test to analyze the treated wood pore structure. The results show that with the increase in the number of cycles, the phosphate deposited on the surface of the wood increases, and the cumulative pore volume and water absorption rate of the wood after 10 cycles are 54.3% and 13.75% lower than that of untreated wood respectively. In addition, the cone calorimeter (CONE) confirmed that the total heat release (THR) and total smoke production (TSP) of wood treated in 10 cycles have decreased by 48.7% and 54.2% respectively compared with the untreated wood. Hence, this treatment method not only improves the mechanical properties of wood. It also improves fire resistance.

Database application is at the core of most web application systems such as web-based email, source codes repository management, public scientific data repository management, news portals, and publication repository of various fields. However, the usage of these database systems for data and information retrieval is severely limited because of lacking support for processing search queries expressed in a natural language (NL). Most web interfaces for databases today only take search queries entered in some form of logical combination of keywords or text strings, which restrict the scope and depth of what a web user really wants to search for, even though natural language based data or information retrieval has made significant advances in recent years. To overcome or at least to alleviate such limitation in web information services, we propose in this article an improved neural model based on an existing framework IRNet for NL query of databases, in which a representation of Gated Graph Neural Network (GGNN) is introduced to encode the database entities and relations. We also represent and use the database values in the prediction model to identify and match table and column names for automatic synthesize a correct SQL statement from a query expressed in a NL sentence. Experiments with a public dataset demonstrates the promising potential of our approach.

Innate DNA sensors detect foreign and endogenous DNA to induce responses to infection and cellular stress or damage. Inappropriate activation by self-DNA triggers severe autoinflammatory conditions, including Aicardi-Goutières syndrome (AGS) that can be caused by defects of the cytosolic DNase 3’repair exonuclease 1 (TREX1). TREX1 loss-of-function alleles are also associated with systemic lupus erythematosus (SLE). Chronic activation of innate antiviral immunity in TREX1-deficient cells depends on the DNA sensor cGAS, implying that accumulating TREX1 DNA substrates cause the inflammatory pathology. Retrotransposon-derived cDNAs were shown to activate cGAS in TREX1-deficient neuronal cells. We addressed other endogenous sources of cGAS ligands in cells lacking TREX1. We find that induced loss of TREX1 in primary cells induces a rapid IFN response that requires ongoing proliferation. The inflammatory phenotype of Trex1-/- mice was partially rescued by additional knock out of exonuclease 1, a multifunctional enzyme providing 5’ flap endonuclease activity for Okazaki fragment processing and postreplicative ribonucleotide excision repair. Our data imply genome replication as a source of DNA waste with pathogenic potential that is efficiently degraded by TREX1.

ObjectiveWe conducted the following cross-sectional study to comprehensively assess the anxiety among Chinese international students who studied online during the COVID-19 pandemic and its influencing factors.MethodsQuestionnaires were distributed through “Sojump,” and a total of 1,090 valid questionnaires were collected. The questionnaire was divided into two parts: general situation and anxiety assessment of students. The former used a self-made questionnaire, and the international general GAD-7 scale was used to measure anxiety. Chi-square test was used to analyze the differences between groups, and logistic regression analysis was performed for the factors with differences.ResultsAnxiety was found in 707 (64.9%) of 1,090 international students. Chi-square test and multivariate Logistic regression analysis showed that the incidence of anxiety was higher in the group under 22 years of age than in the group over 22 years of age (68% vs. 61%, p = 0.015; OR = 1.186, 95% CI 1.045–1.347, p = 0.008); International students living in big cities had a higher incidence of anxiety than those living in rural areas (67% vs. 60%, p = 0.022; OR = 1.419, 95%CI 1.038–1.859, p = 0.011); international students who socialized 3 times or less monthly had a higher incidence of anxiety than those who socialized more than 3 times per month (68% vs. 58%, p = 0.003; OR = 1.52, 95%CI 1.160–1.992, p = 0.002); international students who expected purely online teaching had a higher incidence of anxiety than those who expected purely offline teaching or dual-track teaching (72% vs. 64%, p = 0.037; OR = 1.525, 95%CI 1.069–2.177, p = 0.02); international students with a subjective score of online learning experience of 6 or less had a higher incidence of anxiety than those with subjective scores of more than 6 (70% vs. 60%, p = 0.001, OR = 1.25, 95%CI 1.099–1.422, p = 0.001). However, gender, emotional status, BMI, major of study, vaccination status, and degree type had no significant difference in the incidence of anxiety among international students who studied online during the COVID-19 pandemic.ConclusionDuring COVID-19, international students who were younger, came from big cities, had low social frequency, expected purely online teaching, and had poor experience of online classes were risk factors for anxiety during online classes.