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Abstract The subcortical maternal complex (SCMC) is essential for safeguarding female fertility in mammals. Assembled in oocytes, the SCMC maintains the cleavage of early embryos, but the underlying mechanism remains unclear. Here, we report that 14-3-3, a multifunctional protein, is a component of the SCMC. By resolving the structure of the 14-3-3-containing SCMC, we discover that phosphorylation of TLE6 contributes to the recruitment of 14-3-3. Mechanistically, during maternal-to-embryo transition, the SCMC stabilizes 14-3-3 protein and contributes to the proper control of CDC25B, thus ensuring the activation of the maturation-promoting factor and mitotic entry in mouse zygotes. Notably, the SCMC establishes a conserved molecular link with 14-3-3 and CDC25B in human oocytes/embryos. This study discloses the molecular mechanism through which the SCMC regulates the cell cycle in early embryos and elucidates the function of the SCMC in mammalian early embryogenesis.

Heterogeneous grain structures with coherent L12 nanoprecipitates were constructed in a medium entropy alloy with chemical composition of Co34.5Cr32Ni27.5Al3Ti3 (at. %). The volume fraction and size of L12 nanoprecipitates are observed to become higher and larger, and the interspacing is found to become smaller with increasing aging time, resulting in a severer heterogeneity. The domain of tensile properties was expanded by varying the size and volume fraction of coherent L12 nanoprecipitates after aging treatment. The samples after longer-time aging treatment show stronger strain hardening as compared to those after shorter-time aging treatment. The hetero-deformation-induced (HDI) hardening plays a more vital role in the longer-time aged samples than the shorter-time aged samples, especially at the elasto-plastic transition stage. The dominant precipitation hardening mechanism is observed to transit from dislocation-cutting to Orowan dislocation-looping with increasing precipitation size, as predicted by a theoretical model and validated by experimental results. Multiple deformation defects, such as deformation twins, stacking faults and Lomer-Cottrell locks, are the dominant deformation mechanisms for all samples, while interactions between these defects and L12 nanoprecipitates were observed to be more intensive in the longer-time aged samples than in the shorter-time aged samples, resulting in stronger precipitation and HDI hardening.

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed “Fibrosis overexpression and retention (FORT)”. In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection.

Abstract Objective To identify white matter fiber injury and network changes that may lead to mild cognitive impairment (MCI) progression, then a joint model was constructed based on neuropsychological scales to predict high-risk individuals for Alzheimer's disease (AD) progression among older adults with MCI. Methods A total of 173 MCI patients were included from the Alzheimer's Disease Neuroimaging Initiative(ADNI) database and randomly divided into training and testing cohorts. Forty-five progressed to AD during a 4-year follow-up period. Diffusion tensor imaging (DTI) techniques extracted relevant DTI quantitative features for each patient. In addition, brain networks were constructed based on white matter fiber bundles to extract network property features. Ensemble dimensionality reduction was applied to reduce both DTI quantitative features and network features from the training cohort, and machine learning algorithms were added to construct white matter signature. In addition, 52 patients from the National Alzheimer's Coordinating Center (NACC) database were used for external validation of white matter signature. A joint model was subsequently generated by combining with scale scores, and its performance was evaluated using data from the testing cohort. Results Based on multivariate logistic regression, clinical dementia rating and Alzheimer’s disease assessment scales (CDRS and ADAS, respectively) were selected as independent predictive factors. A joint model was constructed in combination with the white matter signature. The AUC, sensitivity, and specificity in the training cohort were 0.938, 0.937, and 0.91, respectively, and the AUC, sensitivity, and specificity in the test cohort were 0.905, 0.923, and 0.872, respectively. The Delong test showed a statistically significant difference between the joint model and CDRS or ADAS scores (P

Abstract The mislocalization of proteins leads to breast cancer, one of the world’s most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.

Abstract Exosomes derived from mesenchymal stem cells (MSCs) have been confirmed to enhance cell proliferation and improve tissue repair. Exosomes release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression, which is the main pathway through which exosomes exert therapeutic effects. The corresponding process of exosome internalization mainly occurs in the early stage of treatment. However, the therapeutic effect of exosomes in the early stage remains to be further studied. We report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells, serving as an effective method to characterize the therapeutic effect of exosomes. Compared with traditional biochemical methods, we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction force. Through quantitative analysis of traction forces, we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome therapy. Further experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway, thereby promoting cell proliferation. This work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.

Copper is an essential trace element for the human body. Abnormalities in copper metabolism can lead to bone defects, mainly by directly affecting the viability of osteoblasts and osteoclasts and their bone remodeling function, or indirectly regulating bone metabolism by influencing enzyme activities as cofactors. Copper ions released from biological materials can affect osteoblasts and osteoclasts, either directly or indirectly by modulating the inflammatory response, oxidative stress, and rapamycin signaling. This review presents an overview of recent progress in the impact of copper on bone metabolism.Translational potential of this article: The impact of copper on bone metabolism can provide insights into clinical application of copper-containing supplements and biomaterials.

Abstract Background Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the “hotspot region”, which is particularly susceptible to mutation. Methods In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations. Results We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein. Conclusions Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment.

Abstract Assembling graphene sheets into macroscopic fibers with graphitic layers uniaxially aligned along the fiber axis is of both fundamental and technological importance. However, the optimal performance of graphene-based fibers has been far lower than what is expected based on the properties of individual graphene. Here we show that both mechanical properties and electrical conductivity of graphene-based fibers can be significantly improved if bridges are created between graphene edges through covalent conjugating aromatic amide bonds. The improved electrical conductivity is likely due to extended electron conjugation over the aromatic amide bridged graphene sheets. The larger sheets also result in improved π-π stacking, which, along with the robust aromatic amide linkage, provides high mechanical strength. In our experiments, graphene edges were bridged using the established wet-spinning technique in the presence of an aromatic amine linker, which selectively reacts to carboxyl groups at the graphene edge sites. This technique is already industrial and can be easily upscaled. Our methodology thus paves the way to the fabrication of high-performance macroscopic graphene fibers under optimal techno-economic and ecological conditions.

The discovery of covalent H3S and clathrate structure LaH10 with excellent superconducting critical temperatures at high pressures has facilitated a multitude of research on compressed hydrides. However, their superconducting pressures are too high (generally above 150 GPa), thereby hindering their application. In addition, making room-temperature superconductivity close to ambient pressure in hydrogen-based superconductors is challenging. In this work, we calculated the chemically “pre-compressed” Be-H by heavy metals Th and Ce to stabilize the superconducting phase near ambient pressure. An unprecedented ThBeH8 (CeBeH8) with a “fluorite-type” structure was predicted to be thermodynamically stable above 69 GPa (76 GPa), yielding a Tc of 113 K (28 K) decompressed to 7 GPa (13 GPa) by solving the anisotropic Migdal–Eliashberg equations. Be-H vibrations play a vital role in electron–phonon coupling and structural stability of these ternary hydrides. Our results will guide further experiments toward synthesizing ternary hydride superconductors at mild pressures.

A novel alloy composition design (Fe–14Cr–13Co–5Mo–2Ni–1W–1V-0.16C-0.12Nb-0.074Si-0.027Mn, wt. %) was proposed for modification on that of the conventional CSS-42L stainless steel. The present homogeneous structure without carburizing displays an excellent synergy of yield strength and fracture toughness, which should improve the performance of the corresponding case-carburized steels under the contact/bending fatigue conditions. An ultrahigh surface hardness (71 HRC) and an excellent hardness gradient along the depth are achieved in the present case-carburized gradient structure. Higher surface hardness at a temperature range of 200–400 °C is also observed in the present case-carburized gradient structure, as compared to the other case-carburized advanced bearing/gear steels, such as the M50 steel, the M50NiL steel and the conventional CSS-42L steel. Besides the previously reported M6C carbides in the case-carburized conventional CSS-42L steel, M7C3 carbides are newly discovered in the present case-carburized gradient structure due to the novel chemical design. The ultrahigh surface hardness at both room and high temperatures and the excellent hardness gradient distribution in the present case-carburized gradient structure should be attributed to the increased amount of dual-carbides, as well as the ultrafine dual-carbides embedded in the ultrafine martensite matrix. The superior mechanical properties of the present case-carburized gradient structure should be desirable for real bearing/gear applications.

Abstract Excitons in two-dimensional (2D) semiconductors have offered an attractive platform for optoelectronic and valleytronic devices. Further realizations of correlated phases of excitons promise device concepts not possible in the single particle picture. Here we report tunable exciton “spin” orders in WSe2/WS2 moiré superlattices. We find evidence of an in-plane (xy) order of exciton “spin”—here, valley pseudospin—around exciton filling v ex = 1, which strongly suppresses the out-of-plane “spin” polarization. Upon increasing v ex or applying a small magnetic field of ~10 mT, it transitions into an out-of-plane ferromagnetic (FM-z) spin order that spontaneously enhances the “spin” polarization, i.e., the circular helicity of emission light is higher than the excitation. The phase diagram is qualitatively captured by a spin-1/2 Bose–Hubbard model and is distinct from the fermion case. Our study paves the way for engineering exotic phases of matter from correlated spinor bosons, opening the door to a host of unconventional quantum devices.

BackgroundHigh-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear.MethodsHamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.ResultsThe gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices.ConclusionThe findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.

Summary: The live attenuated yellow fever vaccine (YF17D) has caused controversial safety issues in history with low-yield problems, which has led to a large population being unable to be vaccinated and vaccine shortage in facing recent outbreaks. Here, we report a safer live attenuated vaccine candidate, YF17D-Δ77, which contains 77 nucleotides deletion in the 3′ untranslated region (3′ UTR) of the YF17D genome. YF17D-Δ77 exhibited no neurotropism and decreased viscerotropism and caused significantly lower lethality in mice compared to YF17D. Mechanistically, the deletion enhanced the sensitivity of the virus to type I and type II interferon responses, which hindered viral replication. Encouragingly, YF17D-Δ77 provided comparable immune protection in mice as did YF17D. Even 10 PFU of YF17D-Δ77 completely protected mice against YFV-Asibi challenge. In addition, the Δ77 mutation showed excellent stability after successive passages in Vero cells. Collectively, the data suggest that further development of YF17D-Δ77 as vaccine candidate is warranted.

Abstract Achieving superconductivity at room temperature (RT) is a holy grail in physics. Recent discoveries on high‐Tc superconductivity in binary hydrides H3S and LaH10 at high pressure have directed the search for RT superconductors to compress hydrides with conventional electron–phonon mechanisms. Here, an exceptional family of superhydrides is predicated under high pressures, MH12 (M = Mg, Sc, Zr, Hf, Lu), all exhibiting RT superconductivity with calculated Tcs ranging from 313 to 398 K. In contrast to H3S and LaH10, the hydrogen sublattice in MH12 is arranged as quasi‐atomic H2 units. This unique configuration is closely associated with high Tc, attributed to the high electronic density of states derived from H2 antibonding states at the Fermi level and the strong electron–phonon coupling related to the bending vibration of H2 and H‐M‐H. Notably, MgH12 and ScH12 remain dynamically stable even at pressure below 100 GPa. The findings offer crucial insights into achieving RT superconductivity and pave the way for innovative directions in experimental research.

Thin cloud interference presents a significant challenge for the semantic segmentation of optical satellite imagery, which directly degrades the model accuracy and causes difficulties in sample selection. This paper generated a dataset named Populus euphratica and Tamarix chinensis discrimination (PTD), containing both cloudless and thin cloud scenarios. Based on this PTD dataset, an enhanced Atmospheric Scattering Model with Nonlinear Optimization (ASM_NL) was proposed to simulate high-fidelity thin clouds by incorporating two vital nonlinear terms: the point spread function and the Perlin noise. Additionally, we adopt a strategy of mixing simulated thin cloud-covered images (STCI) into the training set at a certain proportion to improve the semantic segmentation accuracy in thin cloud-covered scenarios. The conclusions are as follows: 1) ASM_NL can simulate high-fidelity clouds at an average Jensen-Shannon distance of 0.0699. 2) When dealing with medium- and high-cloud density datasets, mixing STCI proved to be more effective than cloud removal in mitigating thin cloud interference, resulting in average macro F1 score improvements of 0.164 and 0.094, respectively. 3) The semantic segmentation accuracy improved significantly by mixing STCI with a minimal proportion of 1/60, demonstrating the activation of model transfer capabilities. This study provides a concise and efficient methodology for effectively mitigating thin cloud interference in deep learning-based optical satellite imagery analysis.

Summary: Ovarian cancer is a highly lethal gynecological malignancy, emphasizing the need for effective treatment strategies. This study investigated the synergistic effects of quercetin and paclitaxel on ovarian cancer. Using SKOV3 and A2780 cell lines, we found that the combined treatment significantly enhanced cell apoptosis and inhibited invasion and migration compared to individual treatments. Then, we identified 32 common targets between quercetin/paclitaxel and ovarian cancer, with 29 genes showing differential expression between normal ovarian tissue and ovarian tumor tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that quercetin and paclitaxel modulated cancer-related pathways in ovarian cancer treatment. Mechanistic analysis further discovered that the synergistic effect was mediated by downregulating ERBB2 and BIRC5 and upregulating CASP3 expression. This study provides strong evidence that quercetin enhances the effectiveness of paclitaxel in treating ovarian cancer.

The dual-graded structure with both gradients of grain size and coherent L12 precipitation was applied to a (CoCrNi)96Al3Ti3 medium-entropy alloy for achieving superior tensile properties. Simultaneous improvement on yield strength and uniform elongation is observed in the dual-graded structure at cryogenic temperature, compared to those at room temperature. Stronger hetero-deformation-induced hardening and higher density of geometrically necessary dislocations are observed at cryogenic temperature in both single-grain-size-graded and dual-graded structures. The hardening mechanisms at room temperature are characterized by low density of deformation twins and stacking faults (SFs) on one slip system, while are dominated by high density SFs at two slip systems and formation of Lomer-Cottrell (L-C) locks at cryogenic temperature for the single-graded structure. The hardening mechanisms at both room and cryogenic temperatures are revealed by high density of SFs and L-C locks in the dual-grade structure. These SFs and L-C locks can provide strong hardening themselves as dynamic Hall-Petch effect on one hand, and can interact with coherent L12 precipitates for intense precipitation hardening on the other hand. The better tensile properties for the dual-graded structure at cryogenic temperature should be attributed to a special SF-induced plasticity, i.e., the formation of SF networks and their interactions with nanoprecipitates.

Abstract Background Psoriasis is a chronic immune-mediated skin condition. Although biologic treatments are effective in controlling psoriasis, some patients do not respond or lose response to these therapies. Thus, new strategies for psoriasis treatment are still urgently needed. Double-negative T cells (DNT) play a significant immunoregulatory role in autoimmune diseases. In this study, we aimed to evaluate the protective effect of DNT in psoriasis and explore the underlying mechanism. Methods We conducted a single adoptive transfer of DNT into an imiquimod (IMQ)-induced psoriasis mouse model through tail vein injection. The skin inflammation and IL-17A producing γδ T cells were evaluated. Results DNT administration significantly reduced the inflammatory response in mouse skin, characterized by decreased skin folds, scales, and red patches. After DNT treatment, the secretion of IL-17A by RORc+ γδlow T cells in the skin was selectively suppressed, resulting in an amelioration of skin inflammation. Transcriptomic data suggested heightened expression of NKG2D ligands in γδlow T cells within the mouse model of psoriasis induced by IMQ. When blocking the NKG2D ligand and NKG2D (expressed by DNT) interaction, the cytotoxic efficacy of DNT against RORc+IL17A+ γδlow T cells was attenuated. Using Ccr5 −/− DNT for treatment yielded evidence that DNT migrates into inflamed skin tissue and fails to protect IMQ-induced skin lesions. Conclusions DNT could migrate to inflamed skin tissue through CCR5, selectively inhibit IL-17-producing γδlow T cells and finally ameliorate mouse psoriasis. Our study provides feasibility for using immune cell therapy for the prevention and treatment of psoriasis in the clinic.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

SARS-CoV-2 evolves gradually to cause COVID-19 epidemic. One of driving forces of SARS-CoV-2 evolution might be activation of apolipoprotein B mRNA editing catalytic subunit-like protein 3 (APOBEC3) by inflammatory factors. Here, we aimed to elucidate the effect of the APOBEC3-related viral mutations on the infectivity and immune evasion of SARS-CoV-2. The APOBEC3-related C > U mutations ranked as the second most common mutation types in the SARS-CoV-2 genome. mRNA expression of APOBEC3A (A3A), APOBEC3B (A3B), and APOBEC3G (A3G) in peripheral blood cells increased with disease severity. A3B, a critical member of the APOBEC3 family, was significantly upregulated in both severe and moderate COVID-19 patients and positively associated with neutrophil proportion and COVID-19 severity. We identified USP18 protein, a key molecule centralizing the protein-protein interaction network of key APOBEC3 proteins. Furthermore, mRNA expression of USP18 was significantly correlated to ACE2 and TMPRSS2 expression in the tissue of upper airways. Knockdown of USP18 mRNA significantly decreased A3B expression. Ectopic expression of A3B gene increased SARS-CoV-2 infectivity. C > U mutations at S371F, S373L, and S375F significantly conferred with the immune escape of SARS-CoV-2. Thus, APOBEC3, whose expression are upregulated by inflammatory factors, might promote SARS-CoV-2 evolution and spread via upregulating USP18 level and facilitating the immune escape. A3B and USP18 might be therapeutic targets for interfering with SARS-CoV-2 evolution.

Background: Metagenomic next-generation sequencing (mNGS) of plasma DNA has become an attractive diagnostic method for infectious diseases; however, the rate of false-positive results is high. This study aims to evaluate the diagnostic accuracy of mNGS in plasma versus blood cell samples for immunocompromised children with febrile diseases. Methods: The results of conventional microbiological test (CMT) and mNGS using plasma and blood cells in 106 patients with 128 episodes of febrile diseases from the Department of Hematology/Oncology were analyzed and described. Results: The positivity rates for CMT and mNGS of plasma and blood cells were 35.9 %, 84.4 % and 46.9 %, respectively (P

The mitochondrial calcium uniporter (MCU) occupies a noteworthy position in the regulation of mitochondrial calcium uptake. This study investigated the effects of MCU modulator-mediated mitochondrial calcium on mitochondrial dysfunction, oxidative stress, endogenous enzyme activities, and tenderness during postmortem aging. Spermine, as an activator of MCU, resulted in an increase in mitochondrial calcium levels, not only disrupting mitochondrial morphology but also triggering mitochondrial oxidative stress and downregulation of antioxidant factors. Additionally, the spermine group underwent later activation of calpain and earlier activation of caspases, as well as the myofibril fragmentation index was initially lower and then higher compared with control group, indicating that endogenous enzymes played an indispensable role in different aging periods. Interestingly, the results of the Ru360 (an inhibitor of MCU) group were opposite to those aforementioned findings. Our data provide a novel perspective on the regulatory mechanism of mitochondrial calcium homeostasis mediated by MCU on tenderness.

Background: Asthma, characterized by recurrent wheezing, breathlessness, chest tightness, and coughing, is a major health concern among children and adolescents worldwide, currently affecting more than 5 million children. The increasing prevalence of obesity and overweight among the pediatric population has made the issue of childhood respiratory health more complex. Compared with children of healthy weight, the risk of asthma is higher in overweight and obese children. Zinc, a nutrient that regulates the oxidant-antioxidant balance, has been studied for its potential protective effects against asthma in adults and children. However, the results are controversial, with some studies reporting a beneficial effect and others showing no effect. Therefore, our objective was to assess the correlation between zinc intake from diet and asthma occurrence among children and adolescents who are overweight or obese. Methods: The National Health and Nutrition Examination Survey (NHANES) (2011–2020) provided data on individuals aged ≤20 who were overweight or obese, had asthma, and consumed zinc in their diet. The association between dietary zinc and asthma was evaluated using a variety of statistical methods, including multivariate logistic regression, restricted cubic spline analysis, and subgroup analysis. Results: A total of 4597 pediatrics and adolescents were enrolled, with 20.9% (963/4597) suffering from asthma. After adjusting for all covariates in the multivariate logistic regression, compared with the lowest zinc intake group Q1(≤5.68 mg/day), the adjusted OR values for zinc intake and asthma in Q2 (5.69–8.36 mg/day), Q3 (8.37–11.95 mg/day), and Q4 (≥11.96 mg/day) were 0.78 (95% CI: 0.62–0.98, p = 0.03), 0.76 (95% CI: 0.6∼0.98, p = 0.032), 0.71 (95% CI: 0.53∼0.95, p = 0.022), respectively. Stratified analysis showed no interactive role for dietary zinc intake and asthma in overweight or obese children and adolescents. Conclusions: Dietary zinc intake is inversely associated with asthma in overweight or obese children and adolescents.

Non-obstructive azoospermia (NOA) is a disease characterized by spermatogenesis failure and comprises phenotypes such as hypospermatogenesis, mature arrest, and Sertoli cell-only syndrome. Studies have shown that FA cross-linked anemia (FA) pathway is closely related to the occurrence of NOA. There are FA gene mutations in male NOA patients, which cause significant damage to male germ cells. The FA pathway is activated in the presence of DNA interstrand cross-links; the key step in activating this pathway is the mono-ubiquitination of the FANCD2-FANCI complex, and the activation of the FA pathway can repair DNA damage such as DNA double-strand breaks. Therefore, we believe that the FA pathway affects germ cells during DNA damage repair, resulting in minimal or even disappearance of mature sperm in males. This review summarizes the regulatory mechanisms of FA-related genes in male azoospermia, with the aim of providing a theoretical reference for clinical research and exploration of related genes.

In order to cope with the volatile social environment and organisational change, more and more scholars call on leaders to stimulate subordinate effectiveness to a greater extent with inclusive behaviour. Existing studies focus on the positive impact of inclusive leadership, but ignore its potential negative impact. This study integrates Cognition-affection Personality System Theory to explore the double-edged sword mechanism of inclusive leadership on subordinates’ work behaviour. Through the data analysis of 518 paired questionnaires collected in three stages, the results are as follows: Inclusive leadership has a positive impact on subordinates’ psychological entitlement and state gratitude; Psychological entitlement and state gratitude play mediation roles not only between inclusive leadership and work withdrawal behaviour, but also between inclusive leadership and active behaviour; Subordinate narcissistic personality moderates the positive effect of inclusive leadership on psychological entitlement and state gratitude, and then moderates the indirect effect of inclusive leadership on subordinate work withdrawal behaviour and proactive behaviour through psychological entitlement and state gratitude. The above results expand the research on the action mechanism and boundary conditions of inclusive leadership in Chinese organisational context, and provide practical guidance for organisational managers to effectively conduct inclusive leadership.

Abstract Background Ovarian cancer is one of the most common gynecological malignancies due to the lack of early symptoms, early diagnosis and limited screening. Therefore, it is necessary to understand the molecular mechanism underlying the occurrence and progression of ovarian cancer and to identify a basic biomarker for the early diagnosis and clinical treatment of ovarian cancer. Methods The association between FBXO28 and ovarian cancer prognosis was analyzed using Kaplan‒Meier survival analysis. The difference in FBXO28 mRNA expression between normal ovarian tissues and ovarian tumor tissues was obtained from The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) cohorts. The expression levels of the FBXO28 protein in ovarian cancer tissues and normal ovarian tissues were measured via immunohistochemical staining. Western blotting was used to determine the level of FBXO28 expression in ovarian cancer cells. The CCK-8, the colony formation, Transwell migration and invasion assays were performed to evaluate cell proliferation and motility. Results We found that a higher expression level of FBXO28 was associated with poor prognosis in ovarian cancer patients. Analysis of the TCGA and GTEx cohorts showed that the FBXO28 mRNA level was lower in normal ovarian tissue samples than in ovarian cancer tissue samples. Compared with that in normal ovarian tissues or cell lines, the expression of FBXO28 was greater in ovarian tumor tissues or tumor cells. The upregulation of FBXO28 promoted the viability, proliferation, migration and invasion of ovarian cancer cells. Finally, we demonstrated that FBXO28 activated the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer. Conclusions In conclusion, FBXO28 enhanced oncogenic function via upregulation of the TGF-beta1/Smad2/3 signaling pathway in ovarian cancer.

The upper Yellow River water conservation area is an important section for ecological protection and high-quality social-economic development in the Yellow River Basin.The impact of climate change on the spatio-temporal distribution of its water resources will exacerbate the occurrence of natural disasters， which in turn will affect China's regional ecology and even the living environment of human beings.Based on the CN05.1 gridded air temperature， precipitation， and wind speed data from 1961 to 2016 and the actual evaporation data of GLEAM V3.5a from 1981 to 2020， this paper analyzed the changes of key climatic elements in the water conservation area of the upper Yellow River Basin in the past 60 years.The results are as follows： （1） The air temperature in the research area increased significantly， the variation trend of the air temperature can reach 0.34 °C·（10a）-1， and the largest temperature rise occurred in winter.Maqu county and surrounding areas in Heihe region have seen the most dramatic warming.（2） The regional precipitation increased as a whole， the variation trend of the precipitation is about 9.3 mm·（10a）-1.The growth rate was relatively rapid in spring and summer， and the slowest occurred in winter.The growth trend gradually decreased from the northwest to the southeast， with a significant increase in the arid regions of the west， and a relative decreasing trend in the humid regions of the southeast.（3） After experienced an anomalous rise in the early 1970s， the near-surface wind speed continued to decline， the variation trend of it is about -0.11 m·s-1·（10a）-1， and the wind speed decreased in most regions of the study area， especially in the northern Datong River area.（4） The actual evaporation showed an increasing trend， the variation trend of it is 11.89 mm·（10a）-1， of which the relatively large increases occurred in spring and winter， and the growth rate showed a trend of gradual increasing from east to west.Among them， the increase of the actual evaporation in Zhaling Lake， Eling Lake area and the western part of Datong River area was the most significant， and only a few places in the middle and southeast decreased.（5） From the perspective of precipitation and evaporation， the growth rate of precipitation is slightly higher than that of the actual evaporation during the same period （from 1981 to 2016）， therefore the water conservation area in the upper reaches of the Yellow River Basin also has the trends of warming and wetting as the climate warms.

Abstract PUF proteins are characterized by globular RNA-binding domains. They also interact with partner proteins that modulate their RNA-binding activities. Caenorhabditis elegans PUF protein fem-3 binding factor-2 (FBF-2) partners with intrinsically disordered Lateral Signaling Target-1 (LST-1) to regulate target mRNAs in germline stem cells. Here, we report that an intrinsically disordered region (IDR) at the C-terminus of FBF-2 autoinhibits its RNA-binding affinity by increasing the off rate for RNA binding. Moreover, the FBF-2 C-terminal region interacts with its globular RNA-binding domain at the same site where LST-1 binds. This intramolecular interaction restrains an electronegative cluster of amino acid residues near the 5′ end of the bound RNA to inhibit RNA binding. LST-1 binding in place of the FBF-2 C-terminus therefore releases autoinhibition and increases RNA-binding affinity. This regulatory mechanism, driven by IDRs, provides a biochemical and biophysical explanation for the interdependence of FBF-2 and LST-1 in germline stem cell self-renewal.

The conducive conditions of warm and humid climates can facilitate mold proliferation and subsequent mycotoxin production during food processing and distribution, thereby posing a potential risk to consumer health. However, there exists a significant lack of research regarding the diversity of molds and the presence of ochratoxin A (OTA) and patulin (PAT) in food products available in the Yangzhou market. This study was conducted to assess OTA contamination levels and fungal presence in 57 cereal-based food samples, as well as PAT contamination levels and fungal presence in 50 types of foods, including apples, hawthorn berries, pears, and their derivatives. Ochratoxin A (OTA) was detected in 17 out of 57 cereal-based food samples, with concentrations ranging from 0.93 to 32.69 μg/kg. The contamination rate was determined to be 31.48%, and no samples exceeded the established regulatory limits. Furthermore, seven apple products were identified as contaminated with patulin (PAT), exhibiting concentrations between 26.85 and 192.78 μg/kg. Additionally, three food samples derived from hawthorn showed PAT contamination levels ranging from 29.83 to 88.56 μg/kg. Through purification on potato dextrose agar (PDA) medium, observation of colony morphology, and analysis of internal transcribed spacer (ITS) sequences, a total of 35 fungal strains belonging to 13 genera were identified in cereal-based foods. The predominant genera in cereals included Talaromyces, Fusarium, Aspergillus, and Penicillium. Additionally, twelve fungal strains from five genera (Penicillium, Cladosporium, Aureobasidium, Curvularia, and Alternaria) were isolated and identified in fruits and their derivatives. The findings indicate that OTA and PAT toxins are one of the important risk factors that threaten consumer health. Furthermore, the contamination of some other toxigenic strains is also a matter of substantial concern, with potential implications for consumer health.

As the competition intensifies in enhancing the integration and performance of integrated circuits, in accordance with the famous Moore’s Law, higher performance and smaller size requirements are imposed on the dielectric layers in electronic devices. Compared to vacuum methods, the production cost of preparing dielectric layers via solution methods is lower, and the preparation cycle is shorter. This paper utilizes a low-temperature self-exothermic reaction based on the solution method to prepare high-performance Al2O3 dielectric thin films that are compatible with flexible substrates. In this paper, we first established two non-self-exothermic systems: one with pure aluminum nitrate and one with pure aluminum acetylacetonate. Additionally, we set up one self-exothermic system where aluminum nitrate and aluminum acetylacetonate were mixed in a 1:1 ratio. Tests revealed that the leakage current density and dielectric constant of the self-exothermic system devices were significantly optimized compared to the two non-self-exothermic system devices, indicating that the self-exothermic reaction can effectively improve the quality of the dielectric film. This paper further established two self-exothermic systems with aluminum nitrate and aluminum acetylacetonate mixed in 2:1 and 1:2 ratios, respectively, for comparison. The results indicate that as the proportion of aluminum nitrate increases, the overall dielectric performance of the devices improves. The best overall performance occurs when aluminum nitrate and aluminum acetylacetonate are mixed in a ratio of 2:1: The film surface is smooth without cracks; the surface roughness is 0.747 ± 0.045 nm; the visible light transmittance reaches up to 98%; on the basis of this film, MIM devices were fabricated, with tested leakage current density as low as 1.08 × 10−8 A/cm2 @1 MV and a relative dielectric constant as high as 8.61 ± 0.06, demonstrating excellent electrical performance.

The technology for object detection in remote sensing images finds extensive applications in production and people’s lives, and improving the accuracy of image detection is a pressing need. With that goal, this paper proposes a range of improvements, rooted in the widely used YOLOv7 algorithm, after analyzing the requirements and difficulties in the detection of remote sensing images. Specifically, we strategically remove some standard convolution and pooling modules from the bottom of the network, adopting stride-free convolution to minimize the loss of information for small objects in the transmission. Simultaneously, we introduce a new, more efficient attention mechanism module for feature extraction, significantly enhancing the network’s semantic extraction capabilities. Furthermore, by adding multiple cross-layer connections in the network, we more effectively utilize the feature information of each layer in the backbone network, thereby enhancing the network’s overall feature extraction capability. During the training phase, we introduce an auxiliary network to intensify the training of the underlying network and adopt a new activation function and a more efficient loss function to ensure more effective gradient feedback, thereby elevating the network performance. In the experimental results, our improved network achieves impressive mAP scores of 91.2% and 80.8% on the DIOR and DOTA version 1.0 remote sensing datasets, respectively. These represent notable improvements of 4.5% and 7.0% over the original YOLOv7 network, significantly enhancing the efficiency of detecting small objects in particular.

Abstract Background and aim Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (EBV-IM) share mimic symptoms in the early stages of childhood development. We aimed to examine the clinical features and laboratory indices of these two diseases in children and uncover unique indicators to assist pediatricians in identifying these diseases early. Methods We collected clinical data from 791 pediatric patients diagnosed with EBV-IM or EBV-HLH, compared the clinical traits and laboratory biomarkers presented in the two groups, and constructed predictive models based on them. Results Patients with EBV-IM had greater ratios of cervical lymphadenopathy, eyelid edema, and tonsillitis, whereas individuals with EBV-HLH were more likely to have hepatomegaly and splenomegaly. When using the criteria of interleukin (IL)-10 > 89.6 pg/mL, interferon (IFN)-γ > 45.6 pg/mL, ferritin > 429 μg/L, D-dimer > 3.15 mg/L and triglycerides > 2.1 mmol/L, the sensitivity was 87.9%, 90.7%, 98.1%, 91.1% and 81.5% to predict EBV-HLH, while the specificity was 98.4%, 96.3%, 96.5%, 94.1% and 80.6%, respectively. A logistic regression model based on four parameters (IL-10, ferritin, D-dimer, and triglycerides) was established to distinguish EBV-HLH patients from EBV-IM patients, with a sensitivity of 98.0% and a specificity of 98.2%. Conclusions IL-10, IFN-γ, ferritin and D-dimer levels are significantly different between EBV-HLH and EBV-IM. Predictive models based on clinical signs and laboratory findings provide simple tools to distinguish the two situations.

The uptake and degradation mechanisms of dibutyl phthalate (DBP) by three wetland plants, namely Lythrum salicaria, Thalia dealbata, and Canna indica, were studied using hydroponics. The results revealed that exposure to DBP at 0.5 mg/L had no significant effect on the growth of L. salicaria and C. indica but inhibited the growth of T. dealbata. After 28 days, DBP concentrations in the roots of L. salicaria, T. dealbata, and C. indica were 8.74, 5.67, and 5.46 mg/kg, respectively, compared to 2.03–3.95 mg/kg in stems and leaves. Mono-n-butyl phthalate concentrations in L. salicaria tissues were significantly higher than those in the other two plants at 23.1, 15.0, and 13.6 mg/kg in roots, stems, and leaves, respectively. The roots of L. salicaria also had the highest concentration of phthalic acid, reaching 2.45 mg/kg. Carboxylesterase, polyphenol oxidase, and superoxide dismutase may be the primary enzymes involved in DBP degradation in wetland plants. The activities of these three enzymes exhibited significant changes in plant tissues. The findings suggest L. salicaria as a potent plant for phytoremediation and use in constructed wetlands for the treatment of DBP-contaminated wastewater. HIGHLIGHTS The uptake and degradation mechanisms of DBP by three common wetland plants were investigated by the hydroponic experiment.; The uptake and degradation capacities of DBP were higher in L. salicaria, which could well resist the oxidative damage caused by DBP and degrade it under the effect of enzymes.; L. salicaria can be used as a potential plant for DBP removal in phytoremediation and the constructed wetland.;

Aims: To determine the safety and efficacy of microwave ablation (MWA) and transarterial chemoembolization (TACE) with doxorubicin hydrochloride liposome (DHL) in patients with primary liver cancer (PLC) and metastatic liver cancer (MLC). Materials and methods: The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed. Treatment-related adverse events (AEs) were recorded. Local tumor response was evaluated according to the modified RECIST criteria. Local tumor progression-free survival (LTPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Altogether, 96 patients with liver cancer were included (PLC, n ​= ​45; MLC, n ​= ​51). Forty (41.7%) patients experienced AEs during treatment, and eight (8.3%) patients developed grade 3 AEs. Compared to before treatment, the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment. The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC. The median OS was not reached in patients with PLC or MLC. The 1-month and 3-month disease control rates reached more than 80% in both groups. Conclusion: MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Abstract Esophageal squamous precancerous lesions (ESPL) are the precursors of esophageal squamous cell carcinoma (ESCC) including low-grade and high-grade intraepithelial neoplasia. Due to the absence of molecular indicators, which ESPL will eventually develop into ESCC and thus should be treated is not well defined. Indicators, for predicting risks of ESCC at ESPL stages, are an urgent need. We perform spatial whole-transcriptome atlas analysis, which can eliminate other tissue interference by sequencing the specific ESPL regions. In this study, the expression of TAGLN2 significantly increases, while CRNN expression level decreases along the progression of ESCC. Additionally, TAGLN2 protein level significantly increases in paired after-progression tissues compared with before-progression samples, while CRNN expression decreases. Functional studies suggest that TAGLN2 promotes ESCC progression, while CRNN inhibits it by regulating cell proliferation. Taken together, TAGLN2 and CRNN are suggested as candidate indicators for the risk of ESCC at ESPL stages.

Autophagy, a lysosomal self-degradation pathway, plays a critical role in cellular homeostasis by degrading endogenous damaged organelles and protein aggregates into recyclable biological molecules. Additionally, it detoxifies extracellular toxic substances, including drugs and toxic materials, thereby preserving the stability of the intracellular environment. The swift progression of nanotechnology has led to an increased focus on understanding the relationship between nanomaterials and autophagy. The effects of various nanomaterials and nano drug delivery systems on autophagy and their biological functions have been preliminarily assessed, revealing that modulation of intracellular autophagy levels by these agents represents a novel cellular response mechanism. Notably, autophagy regulation based on nanomaterials or nano drug delivery systems for a range of diseases is currently the subject of extensive research. Given the close association between autophagy levels and tumors, the regulation of autophagy has emerged as a highly active area of research in the development of innovative tumor therapies. This review synthesizes the current understanding of the application of nanomaterials or nano drug delivery systems on autophagy and their potential biological functions, suggesting a new avenue for nanomaterial-based autophagy regulation.

This study proposes a fusion algorithm based on forward linear prediction (FLP) and particle swarm optimization–back propagation (PSO-BP) to compensate for the temperature drift. Firstly, the accelerometer signal is broken down into several intrinsic mode functions (IMFs) using variational modal decomposition (VMD); then, according to the FE algorithm, the IMF signal is separated into mixed components, temperature drift, and pure noise. After that, the mixed noise is denoised by FLP, and PSO-BP is employed to create a model for temperature adjustment. Finally, the processed mixed noise and the processed IMFs are rebuilt to obtain the enhanced output signal. To confirm that the suggested strategy works, temperature experiments are conducted. After the output signal is processed by the VMD-FE-FLP-PSO-BP algorithm, the acceleration random walk has been improved by 23%, the zero deviation has been enhanced by 24%, and the temperature coefficient has been enhanced by 92%, compared with the original signal.

UAV remote sensing (RS) image object detection is a very valuable and challenging technology. This article discusses the importance of key features and proposes an object detection network (URSNet) based on a bidirectional multi-span feature pyramid and key feature capture mechanism. Firstly, a bidirectional multi-span feature pyramid (BMSFPN) is constructed. In the process of bidirectional sampling, bicubic interpolation and cross layer fusion are used to filter out image noise and enhance the details of object features. Secondly, the designed feature polarization module (FPM) uses the internal polarization attention mechanism to build a powerful feature representation for classification and regression tasks, making it easier for the network to capture the key object features with more semantic discrimination. In addition, the anchor rotation alignment module (ARAM) further refines the preset anchor frame based on the key regression features extracted by FPM to obtain high-quality rotation anchors with a high matching degree and rich positioning visual information. Finally, the dynamic anchor optimization module (DAOM) is used to improve the ability of feature alignment and positive and negative sample discrimination of the model so that the model can dynamically select the candidate anchor to capture the key regression features so as to further eliminate the deviation between the classification and regression. URSNet has conducted comprehensive ablation and SOTA comparative experiments on challenging RS datasets such as DOTA-V2.0, DIOR and RSOD. The optimal experimental results (87.19% mAP, 108.2 FPS) show that URSNet has efficient and reliable detection performance.

Abstract Terpenoids are pervasive in nature and display an immense structural diversity. As the largest category of plant secondary metabolites, terpenoids have important socioeconomic value in the fields of pharmaceuticals, spices, and food manufacturing. The biosynthesis of terpenoid skeletons has made great progress, but the subsequent modifications of the terpenoid framework are poorly understood, especially for the functionalization of inert carbon skeleton usually catalyzed by hydroxylases. Hydroxylase is a class of enzymes that plays an important role in the modification of terpenoid backbone. This review article outlines the research progress in the identification, molecular modification, and functional expression of this class of enzymes in the past decade, which are profitable for the discovery, engineering, and application of more hydroxylases involved in the plant secondary metabolism. Graphical Abstract

For a solar photovoltaic power system on a university campus, the electricity generated by the system meets the campus load, and the extra electricity is delivered to the grid. Generally, the price of the photovoltaic system is cheaper than that of the utility power system. The full use of solar electricity can reduce the electricity cost of the school. The deep belief network is used to predict solar photovoltaic generation and electricity load, and the gap is found. According to the gap, the power loads on the campus are adjusted to improve the utilization rate of solar power generation. Through the practical application of Changqing Campus of Qilu University of Technology in China, it is found that the utilization rate of solar photovoltaic power generation effectively improved from 91.24% in 2017 to 98.16% in 2019, and the annual electricity is saved by 68 610 yuan (in 2019).

Abstract Infrared (IR) drying is an effective method for the preservation and processing of carmine radish (Raphanus sativus L.). This study aimed to investigate the effects of different IR radiation intensities (2125, 2780, and 3358 W/m2) on the drying properties and flavor components of carmine radish slices. As the IR radiation intensity and the drying temperature increased, the total drying time, the moisture content, and the dehydration rate reduced continuously, while the hardness of carmine radish slices decreased and then increased. Drying at a radiation intensity of 2780 and 3358 W/m2 reduced 50% and 70% of the drying time compared to that of 2125 W/m2, respectively. Flavor components of carmine radish showed apparent changes during the IR drying process with a radiation intensity of 2125 W/m2. IR drying at a lower intensity was beneficial to the retention of volatile flavor components. The retention of volatile substances at an intensity of 2125 W/m2 for 15 min was 1.97 and 1.68 times that for 30 min and control samples, respectively. Consequently, to retain good processing quality and flavor properties of carmine radish slices, the optimal drying parameter of IR within this study was an IR radiation intensity of 2125 W/m2 for about 15 min.

Abstract Background Colorectal cancer (CRC) is the third leading cause of cancer‐related deaths worldwide. Studies have shown that the DNA damage response (DDR) mutation is strongly associated with microsatellite instability (MSI) status and is an indication for patients with CRCs receiving immune checkpoint inhibitor (ICI) treatment. However, DDR mutation in microsatellite stable (MSS) CRC remains unclear. Methods In this study, Fisher's exact test, Student'st‐test, Wilcoxon rank‐sum test and Cox proportional hazards regression model were performed, and a p value of

Abstract Introduction Gastroesophageal varices (GOV) bleeding is a common and serious complication of advanced liver cirrhosis with a median survival of less than 2 years. Multiple guidelines have pointed out that transjugular intrahepatic portosystemic shunt (TIPS) is the rescue treatment of acute variceal hemorrhage (AVB) after failure of standard therapy and an effective second-line treatment for preventing patients with high risks from rebleeding of GOV. The safety and stability of TIPS have been greatly improved due to the improvements of related technologies and the emergence of various novel devices, but the incidence of hepatic encephalopathy (HE) after shunting (10–50%) hindered the widespread use of TIPS. The target portal vein branch might affect the incidence of HE after TIPS. The aim of this study is to compare the rate of HE in patients with hepatitis B virus (HBV) related cirrhosis receiving TIPS either the left or right branch of the portal vein with 8mm Viatorr stent for preventing rebleeding from GOV. Methods and analysis This study is a multicenter randomized controlled trial comparing the influence of shunting left or right portal vein branch on post-TIPS hepatic encephalopathy for preventing rebleeding from GOV in patients with HBV-related cirrhosis. A total of 130 patients will be recruited over a period of 24 months across 5 centers in China. Eligible patients will be stratified 1:1 to constructing either a left or right portal vein shunt with an 8-mm Viatorr stent. The primary objective was to compare the incidence of post-TIPS hepatic encephalopathy between the two groups. The secondary objectives were to compare the grade and duration of hepatic encephalopathy, the rate of shunt dysfunction, the rate of variceal rebleeding, the HE-free survival, the cumulative patency rate of the stent, and the overall survival at 12 months and 24 months between two groups. Ethics and dissemination This study was approved by the ethics committee of Zhongshan Hospital of Fudan University (No. B2018-292R) and was registered at ClinicalTrials.gov (NCT03825848). All participants give written informed consent. Trial registration ClinicalTrials.gov NCT03825848. Registered on January 31, 2019 Trial status The first patient was recruited into our study on June 19, 2019. A total of 55 patients were recruited till May 27, 2021 (27 and 28 patients assigned to shunting the left (L Group) and right (R Group) branches of the portal vein, respectively).

Water is the most abundant molecule found on the earth's surface and is a key factor in multiscale rock destruction. However, given the fine-grained nature of rock and the complexity of its internal structure, the microstructural evolution of rock under the action of water has not yet been elucidated in detail, and little is understood about the relationship between the rock structure and solid–liquid unit. A variety of techniques were used in this study to track the mechanical properties, pore and crack characteristics, and mineral structure degradation characteristics of sandstone at different stages under the action of deionized water, and the evolution mechanisms of the microstructure were analyzed at the molecular scale. The results showed that during the water–rock interaction process, water was adsorbed onto the surface of dolomite minerals and the hydrophilic surface of clay minerals, forming a high-density hydrogen bond network. However, different mineral surface structures had different water adsorption structures, resulting in the strain of the dense clay mineral aggregates under expansion action. Stress concentrated at crack tips under the capillary force of dolomite minerals (very weak dolomite dissolution). These effects resulted in a substantial increase in the number of small pores and enhancements in pore–crack connectivity, and the rock strength exhibited varying degrees of decline at different stages of wet-dry cycles. In general, the results of this paper will help to further elucidate the internal connections between molecular-scale and macroscale processes in rock science.

PurposeSarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes.MethodsWe systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results.ResultsTwenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015).ConclusionThe current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.

So far, most studies have focused on exploring the negative effects of narcissistic leadership. However, little attention has been paid to whether narcissistic leadership also has a positive effect. This study is based on Conservation of Resources Theory and reveals that narcissistic leadership has a double-edged sword effect. By using Mplus7.4 software the analysis of 450 employees and their direct leaders’ pairing data collected in three stages, it is found that: narcissistic leadership has a positive effect on employee’ hostility toward supervisor and psychological availability; hostility toward supervisor mediates the relationship between narcissistic leadership and counterproductive work behavior; psychological availability mediates the relationship between narcissistic leadership and organizational citizenship behavior; in addition, environmental uncertainty enhances the positive effect of narcissistic leadership on employee’ hostility toward supervisor and psychological availability, which in turn moderates the indirect effect of narcissistic leadership on counterproductive work behavior through employee’ hostility toward supervisor and on organizational citizenship behavior through psychological availability.

Objectives: Loneliness is thought to be more likely to occur in older people and influences their lives. This study aimed to verify the influence of loneliness in older Chinese people on their attitudes toward informal care, as well as the demographic, social, and economic factors that may cause loneliness. Methods: Data was collected from older P (age: >60 years) using an online questionnaire. Hierarchical linear regression was used to analyze the associations between demographic, social, and economic factors, loneliness, and attitudes toward informal care. Results: Results have shown that cohabitation and family savings could significantly negatively influence loneliness. Educational background and cohabitation could significantly positively influence attitudes toward informal care. However, loneliness could significantly negatively influence attitudes toward informal care. Conclusion: Older people living alone and with worse economic conditions may need attention from the community and society because they are more likely to suffer from loneliness. Loneliness may also significantly impact older people’s attitudes toward long-term care. Older people are more likely to feel lonely may have more negative attitudes toward informal care. Communities need to make more efforts to improve community health services or formal care services for these older people to address situations where informal care is not sufficiently provided.

Abstract Background Cushing’s syndrome is known as an important cause of secondary osteoporosis, characterized by reduction of bone mineral density and potential occurrence of fragility fractures before diagnosis in young population. Therefore, for young patients with fragility fractures, especially in young women, more attention should be paid on glucocorticoid excess caused by Cushing’s syndrome, due to relatively higher rate of misdiagnosis, distinct pathological characteristics and different treatment strategies compared with violent fractures and primary osteoporosis related fractures. Case presentation We presented an unusual case of a 26-year-old woman with multiple vertebral compression fractures and pelvis fractures, subsequently diagnosed as Cushing’s syndrome. On admission, the radiographic results showed fresh second lumbar vertebra fracture, and old fourth lumbar vertebra and pelvic fractures. The dual energy X-ray absorptiometry of lumbar spine revealed marked osteoporosis, and her plasm cortisol was extremely high. Then, Cushing’s syndrome, caused by left adrenal adenoma, was diagnosed by further endocrinological and radiographic examinations. After receiving left adrenalectomy, her plasma ACTH and cortisol values returned to normal level. In term of OVCF, we adopted conservative treatments, including pain management, brace treatment, and anti-osteoporosis measures. Three months after discharge, the patient’s low back pain was in complete remission without new onset of pain, and returned to normal life and work. Furthermore, we reviewed the literatures on advancements in the treatment of OVCF caused by Cushing’s syndrome, and based on our experiences, proposed some additional perspectives to guide treatment. Conclusion In term of OVCF secondary to Cushing’s syndrome without neurological damage, we prefer systematic conservative treatments, including pain management, brace treatment, and anti-osteoporosis measures, to surgical treatment. Among them, anti-osteoporosis treatment has the highest priority because of the reversibility of osteoporosis caused by Cushing’s syndrome.