Lipid transfer protein StLTPa enhances potato disease resistance against different pathogens by binding and disturbing the integrity of pathogens plasma membrane.

Potato is the third most important food crop worldwide. Potato production suffers from severe diseases caused by multiple detrimental plant pathogens, and broad-spectrum disease resistance genes are rarely identified in potato. Here we identified the potato non-specific lipid transfer protein StLTPa, which enhances species none-specific disease resistance against various pathogens, such as the oomycete pathogen Phytophthora infestans, the fungal pathogens Botrytis cinerea and Verticillium dahliae, and the bacterial pathogens Pectobacterium carotovorum and Ralstonia solanacearum. The StLTPa overexpression potato lines do not show growth penalty. Furthermore, we provide evidence that StLTPa binds to lipids present in the plasma membrane (PM) of the hyphal cells of P. infestans, leading to an increased permeability of the PM. Adding of PI(3,5)P2 and PI(3)P could compete the binding of StLTPa to pathogen PM and reduce the inhibition effect of StLTPa. The lipid-binding activity of StLTPa is essential for its role in pathogen inhibition and promotion of potato disease resistance. We propose that StLTPa enhances potato broad-spectrum disease resistance by binding to, and thereby promoting the permeability of the PM of the cells of various pathogens. Overall, our discovery illustrates that increasing the expression of a single gene in potato enhances potato disease resistance against different pathogens without growth penalty.

Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p.

BACKGROUND: GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. METHODS: GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments. RESULTS: The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression. CONCLUSION: Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.

Pachymic acid (PA) inhibits ferroptosis of cardiomyocytes via activation of the AMPK in mice with ischemia/reperfusion-induced myocardial injury.

Pachymic acid (PA) is a lanostane-type triterpenoid with various pharmacological effects. However, little is known about the effect of PA on myocardial infarction (MI) induced by ischemia/reperfusion (I/R). In this study, we aimed to investigate the protective effect of PA and its underlying mechanism. A cellular MI model was established by oxygen-glucose deprivation and reperfusion (OGD/R) treatment in HL-1 cardiomyocytes, and we found that OGD/R treatment decreased cell viability and glutathione peroxide (GSH-Px) activity, increased Fe2+ concentration and lactate dehydrogenase (LDH) activity, promoted malondialdehyde (MDA) and reactive oxygen species (ROS) production, and inhibited the expression of ferroptosis marker proteins SLC7A11 and GPX4 in a time-dependent manner. OGD/R-induced HL-1 cells were pretreated with different concentrations of PA (0, 20, 40, 60 µg/mL) for 24 h, and toxicological experiments showed that 150 µg/mL PA decreased cell viability, while low concentrations of PA had no toxic effect on cells. 20 µg/mL PA reversed the inhibitory effect of OGD/R on cell viability, reduced MDA and ROS production, and Fe2+ accumulation, increased GSH-Px activity and the expression of SLC7A11 and GPX4, and decreased LDH activity, especially at 60 µg/mL PA. Meanwhile, PA promoted the phosphorylation of IRS-1, AKT, and AMPK proteins in a dose-dependent manner. AICAR, an AMPK activator, inhibited ferroptosis, while STO-609, an AMPK inhibitor, largely abolished the effect of PA on OGD/R-induced ferroptosis of HL-1 cells. In addition, PA inhibited ferroptosis and myocardial I/R injury in wild-type mice and AMPK knockout (AMPK-/- ) mice. Collectively, PA inhibited ferroptosis of cardiomyocytes through activating of the AMPK pathway, thereby alleviating myocardial I/R injury in mice.

Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke.

BACKGROUND: Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient. METHODS: All participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1ß) within 14 days after stroke onset. RESULTS: Eighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score < 2 compared to those who did not receive this treatment (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving edaravone dexborneol injection exhibited lower expression levels of interleukin (IL)-1ß, IL-6, and IL-17, along with higher levels of IL-4 and IL-10 expression during the acute phase of ischemic stroke (P < 0.05). These trends were not observed for IL-2, IL-5, IL-8, IL-12p70, tumor necrosis factor-α, interferon-γ [IFN-γ], and IFN-α (P > 0.05). CONCLUSIONS: Treatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www. CLINICALTRIALS: gov/ct2/show/NCT04175691 .

Hyperglycemia affects axial signs in patients with Parkinson's disease through mechanisms of insulin resistance or non-insulin resistance.

OBJECTIVE: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP). METHODS: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups. Correlations between levels of HbA1c and the homeostatic model assessment (HOMA)-IR and motor function in PWP were further analyzed. RESULTS: HbA1c level was significantly and positively correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score, axial signs subscore, the Timed Get Up and Go test time, the center of pressure displacement of standing with eyes open and closed, and significantly and negatively correlated with the 10-m walk test comfortable gait speed. HOMA-IR level was significantly and negatively correlated with 10-m walk test comfortable gait speed, but not with others. CONCLUSIONS: PWP with high HbA1c showed worse axial symptoms, including dysfunction of automatic walking, dynamic balance, and postural control than those with low HbA1c. In PWP, the effects of hyperglycemia on automatic walking speed may be associated with the IR-related mechanisms, and the effects on dynamic balance and postural control may be related to mechanisms other than IR.

The association between sarcopenia and incident of depressive symptoms: a prospective cohort study.

BACKGROUND: Epidemiological studies have shown that sarcopenia was associated with depression among older adults. However, most of these investigations used a cross-sectional design, limiting the ability to establish a causal relation, the present study examined whether sarcopenia was associated with incident depressive symptoms. METHODS: This is a prospective cohort study with participants from the Western China Health and Aging Trends (WCHAT) study. Participants could complete anthropometric measurements and questionnaires were included. The exposure was sarcopenia, defined according to the Asian Working Group for Sarcopenia in 2019, the outcome was depressive symptoms, evaluated by GDS-15. We excluded depression and depressive symptoms at baseline and calculated the risk of incident depressive symptoms during the follow-up year. RESULTS: A total of 2612 participants (mean age of 62.14 ± 8.08 years) were included, of which 493 with sarcopenia. 78 (15.82%) participants with sarcopenia had onset depressive symptoms within the next year. After multivariable adjustment, sarcopenia increased the risk of depressive symptoms (RR = 1.651, 95%CI = 1.087-2.507, P = 0.0187) in overall participants. Such relationship still exists in gender and sarcopenia severity subgroups. Low muscle mass increased the risk of depressive symptoms (RR = 1.600, 95%CI = 1.150-2.228, P = 0.0053), but low muscle strength had no effect (RR = 1.250, 95%CI = 0.946-1.653, P = 0.117). CONCLUSIONS: Sarcopenia is an independent risk factor for depressive symptoms, Precautions to early detect and targeted intervene for sarcopenia should continue to be employed in adult with sarcopenia to achieve early prevention for depression and reduce the incidence of adverse clinical outcomes.

Establishment of cerebral perfusion in a rat model with extracorporeal life support.

Background: Extracorporeal life support echniques as an Adjunct to Advanced Cardiac Life Support is usually suitable for complex heart surgery such as cardiopulmonary bypass (CPB). Cerebral perfusion is a clinically feasible neuroprotective strategy; however, the lack of a reliable small animal model.Methods: Based on the rat model of ECLS we evaluate the effects of ECLS-CP using HE staining, Nissl staining, TUNEL staining and ELISA.Result: We found that ECLS combined with the cerebral perfusion model did not cause brain injury and immune inflammation. There was no difference between the two by a left carotid artery or right carotid artery CP.Conclusion: These experimental results can provide the experimental basis for selecting blood vessels for ECLS patients and clinical CP to offers a trustworthy animal model for future exploration of applying brain perfusion strategies during ECLS-CP.

Transcription Factors and Their Regulatory Roles in the Male Gametophyte Development of Flowering Plants.

Male gametophyte development in plants relies on the functions of numerous genes, whose expression is regulated by transcription factors (TFs), non-coding RNAs, hormones, and diverse environmental stresses. Several excellent reviews are available that address the genes and enzymes associated with male gametophyte development, especially pollen wall formation. Growing evidence from genetic studies, transcriptome analysis, and gene-by-gene studies suggests that TFs coordinate with epigenetic machinery to regulate the expression of these genes and enzymes for the sequential male gametophyte development. However, very little summarization has been performed to comprehensively review their intricate regulatory roles and discuss their downstream targets and upstream regulators in this unique process. In the present review, we highlight the research progress on the regulatory roles of TF families in the male gametophyte development of flowering plants. The transcriptional regulation, epigenetic control, and other regulators of TFs involved in male gametophyte development are also addressed.

Theoretical Study and Analysis of CsSnX3 (X = Cl, Br, I) All-Inorganic Perovskite Solar Cells with Different X-Site Elements.

In this research, SCAPS-1D simulation software (Version: 3.3.10) was employed to enhance the efficiency of CsSnX3 (X = Cl, Br, I) all-inorganic perovskite solar cells. By fine-tuning essential parameters like the work function of the conductive glass, the back contact point, defect density, and the thickness of the light absorption layer, we effectively simulated the optimal performance of CsSnX3 (X = Cl, Br, I) all-inorganic perovskite solar cells under identical conditions. The effects of different X-site elements on the overall performance of the device were also explored. The theoretical photoelectric conversion efficiency of the device gradually increases with the successive substitution of halogen elements (Cl, Br, I), reaching 6.09%, 17.02%, and 26.74%, respectively. This trend is primarily attributed to the increasing size of the halogen atoms, which leads to better light absorption and charge transport properties, with iodine (I) yielding the highest theoretical conversion efficiency. These findings suggest that optimizing the halogen element in CsSnX3 can significantly enhance device performance, providing valuable theoretical guidance for the development of high-efficiency all-inorganic perovskite solar cells.

Accessible New Non-Quantum Dot Cs2PbI2Cl2-Based Photocatalysts for Efficient Hole-Driven Photocatalytic Applications.

Efficient, low-cost photocatalysts with mild synthesis conditions and stable photocatalytic behavior have always been the focus in the field of photocatalysis. This study proves that non-quantum-dot Cs2PbI2Cl2-based materials, created by a simple method, can be successfully employed as new high-efficient photocatalysts. The results demonstrate that two-dimensional Cs2PbI2Cl2 perovskite can achieve over three times higher photocatalytic performance compared to three-dimensional CsPbBr3 perovskite. Moreover, the photocatalytic performance of Cs2PbI2Cl2 can be further improved by constructing a heterojunction structure, such as Cs2PbI2Cl2/CsPbBr3. Cs2PbI2Cl2 can connect well with CsPbBr3 through a simple method, resulting in tight bonding at the interface and efficient carrier transfer. Cs2PbI2Cl2/CsPbBr3 exhibits notable 5-fold and 10-fold improvements in photocatalytic performance and rate compared to CsPbBr3. Additionally, Cs2PbI2Cl2/CsPbBr3 demonstrates superb stable catalytic performance, with nearly no decrease in photocatalytic performance after 7 months (RH = 20% ± 10, T = 25 °C ± 5). This study also reveals that the photocatalytic process based on Cs2PbI2Cl2/CsPbBr3 can directly oxidize organic matter using holes, without relying on the generation of intermediate reactive oxygen species from water or oxygen (such as ·OH or ·O2-), showcasing further potential for achieving high photocatalytic efficiency and selectivity in anhydrous/anaerobic catalytic reactions and treating recalcitrant pollutants.

New Copper Complexes with N,O-Donor Ligands Based on Pyrazole Moieties Supported by 3-Substituted Acetylacetone Scaffolds.

The new 3-monosubstituted acetylacetone ligands, 3-(phenyl(1H-pyrazol-1-yl)methyl)pentane-2,4-dione (HLacPz) and 3-((3,5-dimethyl-1H-pyrazol-1-yl)(phenyl)methyl)pentane-2,4-dione (HLacPzMe), were synthesized and used as supporting ligands for new copper(II) and copper(I) phosphane complexes of the general formulae [Cu(HLacX)2(LacX)2] and [Cu(PPh3)2(HLacX)]PF6 (X = Pz (pyrazole) or PzMe (3,5-dimethylpyrazole)), respectively. In the syntheses of the Cu(I) complexes, the triphenylphosphine coligand (PPh3) was used to stabilize copper in the +1 oxidation state, avoiding oxidation to Cu(II). All compounds were characterized by CHN analysis, 1H-NMR, 13C-NMR, FT-IR spectroscopy, and electrospray ionization mass spectrometry (ESI-MS). The ligands HLacPz (1) and HLacPzMe (2) and the copper complex [Cu(PPh3)2(HLacPz)]PF6 (3) were also characterized by X-ray crystallography. The reactivity of these new compounds was investigated and the new compounds 4-phenyl-4-(1H-pyrazol-1-yl)butan-2-one (7) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-4-phenylbutan-2-one (8) were obtained in basic conditions via the retro-Claisen reaction of related 3-monosubstituted acetylacetone, providing efficient access to synthetically useful ketone compounds. Compound 8 was also characterized by X-ray crystallography.

Temperature-dependent toxicity of fluoxetine alters the thermal plasticity of marine diatoms.

Anthropogenic activities have led to the emergence of pharmaceutical pollution in marine ecosystems, posing a significant threat to biodiversity in conjunction with global climate change. While the ecotoxicity of human drugs on aquatic organisms is increasingly recognized, their interactions with environmental factors, such as temperature, remain understudied. This research investigates the physiological effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on two diatom species, Phaeodactylum tricornutum and Thalassiosira weissflogii. Results demonstrate that fluoxetine significantly reduces growth rate and biomass production, concurrently affecting pigment contents and the thermal performance curve (TPC) of the diatoms. Fluoxetine reduces the synthesis of chlorophyll a (Chl a) and carotenoid (Car), indicating inhibition of photosynthesis and photoprotection. Furthermore, fluoxetine decreases the maximum growth rate (µmax) while increasing the optimum temperature (Topt) in both species, suggesting an altered thermal plasticity. This shift is attributed to the observed decrease in the inhibition rate of fluoxetine with rising temperatures. These findings emphasize the physiological impacts and ecological implications of fluoxetine on phytoplankton and underscore the significance of considering interactions between multiple environmental drivers when accessing the ecotoxicity of potential pollutants. The present study provides insights into crucial considerations for evaluating the impacts of pharmaceutical pollution on marine primary producers.

Association between the triglyceride glucose index and low skeletal muscle mass: a cross-sectional study.

OBJECTIVES: Triglyceride glucose (TyG) represents a consistent surrogate biomarker and index of insulin resistance (IR), IR has also been linked to skeletal muscle mass loss (SMM-L). Here, we evaluated the association between SMM-L and the TyG index (TyGi). DESIGN: An analytical cross-sectional study. SETTING: Tertiary care hospitals. PARTICIPANTS: 36 275 participants who underwent health checks between 1 January 2013 and 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: A bioelectrical impedance analysis was used to assess the body composition, SMM-L was defined as low ASMI (total limb lean mass/height2) and TyGi was calculated as ln(triglycerides (mg/dL)×fasting blood glucose (mg/dL)/2). RESULTS: A total of 36 275 subjects were included in the study, of which 58.46% were male, with a mean age of 43.74±12.33 years. The prevalence of low skeletal muscle mass (SMM) was 17.7% and the mean TyGi was 8.56±0.64. TyGi was found to be significantly correlated with low SMM in all subjects (OR 1.87, 95% CI 1.75 to 2.00, p<0.001), with higher correlations seen in younger subjects (OR 1.97, 95% CI 1.77 to 2.20, p<0.001), and remaining significant in middle age (OR 1.95, 95% CI 1.77 to 2.14, p<0.001), old age (OR 1.73, 95% CI 1.38 to 1.16, p<0.001), men (OR 1.60, 95% CI 1.46 to 1.76, p<0.001) and women (OR 2.59, 95% CI 2.39 to 2.87, p<0.001). CONCLUSIONS: These data demonstrated a significant independent interaction between TyGi and low SMM in all subjects regardless of sex and age subgroups in the general population.

Modulating macrophage-mediated programmed cell removal: An attractive strategy for cancer therapy.

Macrophage-mediated programmed cell removal (PrCR) is crucial for the identification and elimination of needless cells that maintain tissue homeostasis. The efficacy of PrCR depends on the balance between pro-phagocytic "eat me" signals and anti-phagocytic "don't eat me" signals. Recently, a growing number of studies have shown that tumourigenesis and progression are closely associated with PrCR. In the tumour microenvironment, PrCR activated by the "eat me" signal is counterbalanced by the "don't eat me" signal of CD47/SIRPα, resulting in tumour immune escape. Therefore, targeting exciting "eat me" signalling while simultaneously suppressing "don't eat me" signalling and eventually inducing macrophages to produce effective PrCR will be a very attractive antitumour strategy. Here, we comprehensively review the functions of PrCR-activating signal molecules (CRT, PS, Annexin1, SLAMF7) and PrCR-inhibiting signal molecules (CD47/SIRPα, MHC-I/LILRB1, CD24/Siglec-10, SLAMF3, SLAMF4, PD-1/PD-L1, CD31, GD2, VCAM1), the interactions between these molecules, and Warburg effect. In addition, we highlight the molecular regulatory mechanisms that affect immune system function by exciting or suppressing PrCR. Finally, we review the research advances in tumour therapy by activating PrCR and discuss the challenges and potential solutions to smooth the way for tumour treatment strategies that target PrCR.

Exploring Female Relatives of Patients with Hemophilia' Awareness, Attitudes, and Understanding Towards Genetic Testing.

Purpose: A better understanding of the factors that influence engagement is needed to provide a reference for conducting genetic testing in female relatives of patients with hemophilia (PWH). We therefore determined the perceptions and understanding of genetic testing among female relatives of PWH in China. Methods: We carried out a qualitative study using in-depth, semi-structured interviews with 11 female relatives of PWH in Shanxi Province, China. The resulting data were analyzed using thematic analyses. Results: This study extracted four topics: uncertainty about carrier genetic status; limited understanding of genetic testing; coexistence of positive and negative coping; and multi-aspect demands. Conclusion: Healthcare professionals should provide personalized and multidimensional health education and comprehensive decision-making support to female relatives of PWH, to enhance their motivation and willingness to undergo genetic testing. It is also important to actively improve relevant policies, strengthen the genetic testing service system, and promote the popularization of genetic testing in female relatives of PWH.

Effect of cross-linking density on the rheological behavior of ultra-soft chitosan microgels at the oil-water interface.

In this paper, microgels with uniform particle size were prepared by physically cross-linking the hydrophobically modified chitosan (h-CS) with sodium phytate (SP). The effects of cross-linking density on the interfacial adsorption kinetics, viscoelasticity, stress relaxation, and micorheological properties of the hydrophobically modified chitosan microgels (h-CSMs) at the oil-water interface were extensively investigated by the dilatational rheology, compressional rheology, and particle tracing microrheology. The results were correlated with the particle size, morphology, and elasticity of the microgels characterized by dynamic light scattering and atomic force microscopy. It was found that with the increase of cross-linking density, the h-CSMs changed from a polymer-like state to ultra-soft fussy spheres with higher elastic modulus. The compression isotherms demonstrated multi-stage increase caused by the interaction between the shells and that between the cores of the microgels successively. As the increase of cross-linking density, the h-CSMs diffused slower to the oil-water interface, but demonstrating faster permeation adsorption and rearrangement at the oil-water interface, finally forming interfacial layers of higher viscoelastic modulus due to the core-core interaction. Both the initial tension relaxation and the microgel rearrangement after interface expansion became faster as the microgel elasticity increased. The interfacial microrheology demonstrated dynamic caging effect caused by neighboring microgels. This article provides a more comprehensive understanding of the behaviors of polysaccharide microgels at the oil-water interface.

Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Retrospective study of the clinical manifestations and efficacy of immunotherapy for patients with acquired hemophilia A.

OBJECTIVE: Raising awareness of acquired hemophilia A (AHA) and early diagnosis is critical to reduce the associated mortality rate. We aimed to characterize acquired hemophilia in Chinese patients and evaluate the effectiveness of immunotherapy. METHODS: The clinical characteristics, laboratory test data, therapeutic approaches, and outcomes of 20 patients with AHA who were admitted to Xi'an Central Hospital between January 2012 and December 2020 were retrospectively studied. RESULTS: Nine of the patients (45%) were treated by single glucocorticoid administration; three (15%) with cyclophosphamide (CP) in combination with a glucocorticoid; four individuals (20%) received a combination therapy of rituximab with CP and glucocorticoid or rituximab with CP, vincristine, and a glucocorticoid; three (15%) by injection of human immunoglobulin in combination with a glucocorticoid; and one (5%) with CP alone. Six patients (30%) achieved total remission and 11 (55%) partial remission (PR), but three (15%) did not enter remission, indicating an objective response rate of 85%. CONCLUSION: Combination therapy with rituximab or intravenous human immunoglobulin achieves superior results in some patients with AHA. Immunosuppression and the administration of coagulation factors can rapidly control the disease and are efficacious, but >50% of patients only achieved PR. These findings suggest that the complete elimination of inhibitors requires prolonged immunosuppression therapy.

Decoding silkworm spinning programmed by pH and metal ions.

Silk is one of the toughest fibrous materials known despite spun at ambient temperature and pressure with water as a solvent. It is a great challenge to reproduce high-performance artificial fibers comparable to natural silk by bionic for the incomplete understanding of silkworm spinning in vivo. Here, we found that amphipol and digitonin stabilized the structure of natural silk fibroin (NSF) by a large-scale screening in vitro, and then studied the close-to-native ultrastructure and hierarchical assembly of NSF in the silk gland lumen. Our study showed that NSF formed reversible flexible nanofibrils mainly composed of random coils with a sedimentation coefficient of 5.8 S and a diameter of about 4 nm, rather than a micellar or rod-like structure assembled by the aggregation of globular NSF molecules. Metal ions were required for NSF nanofibril formation. The successive pH decrease from posterior silk gland (PSG) to anterior silk gland (ASG) resulted in a gradual increase in NSF hydrophobicity, thus inducing the sol-gelation transition of NSF nanofibrils. NSF nanofibrils were randomly dispersed from PSG to ASG-1, and self-assembled into anisotropic herringbone patterns at ASG-2 near the spinneret ready for silkworm spinning. Our findings reveal the controlled self-assembly mechanism of the multi-scale hierarchical architecture of NSF from nanofibrils to herringbone patterns programmed by metal ions and pH gradient, which provides novel insights into the spinning mechanism of silk-secreting animals and bioinspired design of high-performance fibers.

Perceived social support mediates the effect of COVID-19 pandemic on job adaptation disorders of workers: An exploratory cross-sectional study.

COVID-19 lockdown can lead to job adaptation disorders, which are heterogeneous among individuals. The purpose of this study was to explore the association between perceived social support and job adaptation disorders among workers in China during the COVID-19 pandemic. The questionnaires of Psychological Questionnaire for Public Health Emergencies, Multidimensional Scale of Perceived Social Support, Work Attitude Scale were used for this cross-section study via an online survey. The study included 626 employees. Hierarchical regression analysis and Bootstrap method were used to investigate the mediation effect of perceived social support between the emergency and job adaptation disorders. The percentages of the 5 dimensions of depression, neurasthenia, fear, compulsion-anxiety, and hypochondria in workers were 59.7%, 56.1%, 92.3%, 42.0%, and 18.7%, respectively. Social support mediated the relationship between depression, neurasthenia, obsessive-compulsive anxiety and job adaptation disorder, accounting for 18.1%, 16.1%, and 17.5% of the total effect (ab/c), respectively. Perceived social support could alleviate COVID-19 pandemic-related depression, neurasthenia, compulsion-anxiety, and job adaptation disorder in Chinese workers. Improving their perception of social support, workers may better adapt themselves to work in the challenging of the public health emergency during COVID-19 pandemic.