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Background: Porous metal materials have been widely studied for applications in orthopedic field, owing to their excellent features and properties in bone healing. Porous metal materials with different compositions, manufacturing methods, and porosities have been developed. Whereas, the systematic mechanisms on how porous metal materials promote bone healing still remain unclear. Methods: This review is concerned on the porous metal materials from three aspects with accounts of specific mechanisms, inflammatory regulation, angiogenesis and osteogenesis. We place great emphasis on different cells regulated by porous metal materials, including mesenchymal stem cells (MSCs), macrophages, endothelial cells (ECs), etc. Result: The design of porous metal materials is diversified, with its varying pore sizes, porosity material types, modification methods and coatings help researchers create the most experimentally suitable and clinically effective scaffolds. Related signal pathways presented from different functions showed that porous metal materials could change the behavior of cells and the amount of cytokines, achieving good influence on osteogenesis. Conclusion: This article summarizes the current progress achieved in the mechanism of porous metal materials promoting bone healing. By modulating the cellular behavior and physiological status of a spectrum of cellular constituents, such as macrophages, osteoblasts, and osteoclasts, porous metal materials are capable of activating different pathways and releasing regulatory factors, thus exerting pivotal influence on improving the bone healing effect. The translational potential of this article: Porous metal materials play a vital role in the treatment of bone defects. Unfortunately, although an increasing number of studies have been concentrated on the effect of porous metal materials on osteogenesis-related cells, the comprehensive regulation of porous metal materials on the host cell functions during bone regeneration and the related intrinsic mechanisms remain unclear. This review summarizes different design methods for porous metal materials to fabricate the most suitable scaffolds for bone remodeling, and systematically reviews the corresponding mechanisms on inflammation, angiogenesis and osteogenesis of porous metal materials. This review can provide more theoretical framework and innovative optimization for the application of porous metal materials in orthopedics, dentistry, and other areas, thereby advancing their clinical utility and efficacy.

Abstract The Hepatitis B core antigen (HBcAg) has been used as a carrier of several heterologous protein fragments based on its capacity to form virus-like particles (VLPs) and to activate innate and adaptive immune responses. In the present work, two chimeric proteins were designed as potential pancorona vaccine candidates, comprising the N- or C- terminal domain of SARS-CoV-2 nucleocapsid (N) protein fused to HBcAg. The recombinant proteins, obtained in E. coli, were named CN-1 and CND-1, respectively. The final protein preparations were able to form 10–25 nm particles, visualized by TEM. Both proteins were recognized by sera from COVID-19 convalescent donors; however, the antigenicity of CND-1 tends to be higher. The immunogenicity of both proteins was studied in Balb/C mice by intranasal route without adjuvant. After three doses, only CND-1 elicited a positive immune response, systemic and mucosal, against SARS-CoV-2 N protein. CND-1 was evaluated in a second experiment mixed with the CpG ODN-39 M as nasal adjuvant. The induced anti-N immunity was significantly enhanced, and the antibodies generated were cross-reactive with N protein from Omicron variant, and SARS-CoV-1. Also, an anti-N broad cellular immune response was detected in spleen, by IFN-γ ELISpot. The nasal formulation composed by CND-1 and ODN-39 M constitutes an attractive component for a second generation coronavirus vaccine, increasing the scope of S protein-based vaccines, by inducing mucosal immunity and systemic broad humoral and cellular responses against Sarbecovirus N protein.

Thermal barrier coatings (TBCs) are commonly used for thermal protection in aero-engine and gas turbine. TBCs are in service under severe environments where high temperatures and high loads, as well as large thermal gradients. Reproducing this service environment of TBCs by in-situ laboratorial setup is essential to the investigation of TBCs failure mechanism. Here we report a thermal gradient mechanical device for the in-situ high-energy synchrotron X-ray diffraction strain measurement. I-shaped samples, with plasma spray physical vapor deposited coatings, were tested with backside cooling and frontside heating under various controlled circumstances. The in-situ strains show that there is a strain gradient within the coating, and the strain change is most pronounced at the topcoat/bond coat interface. Results of this study demonstrate that variations in these conditions create corresponding trends in depth-resolved strains with the largest effects displayed at or near the interface with the bond coat. Temporal- and space-resolved strain distributions of TBCs in near-service environments based on previous studies that have not been publicly reported were obtained, which are essential for the application of validated models of material behavior in extreme environments and for the inverse correction of the preparation process parameters.

Abstract To study the influence of cyclic disturbance stress on the mechanical behavior of coal during mining, a gas containing coal fluid-solid coupling servo seepage experimental system was used to conduct experimental research on the acoustic emission (AE) characteristics of gas containing coal under two stress paths of graded cyclic loading and unloading. The AE characteristics of coal damage and failure processes under different cyclic stress paths were analyzed. The research results indicate that: (1) The overall characteristics of AE signals for both graded cyclic loading and unloading paths are basically the same. With increasing of the amount of graded cyclic loading or unloading, the AE count reaches its maximum value when reaching failure, and the cumulative ringing calculation of AE increases exponentially. (2) The AE signals under the graded cyclic loading or unloading path exhibit obvious zoning characteristics. In the low and medium stress regions, the AE signal basically satisfies the Kaiser effect, while reaching the high stress region before failure, the AE signal exhibits a significant Felicity effect. (3) The concentration coefficient of AE and the intensity coefficient of the Kaiser effect have been newly defined. They are used to quantitatively characterize the extent of the Kaiser effect of AEs under graded cyclic stress. It was found that as the variation of graded cyclic stress increases, the concentration coefficient and Kaiser effect intensity coefficient both show a decreasing trend. (4) Combining the AF and RA values of AE, it was found that the coal failure signals of the two stress paths were basically similar, that is, the overall failure was mainly tensile failure, and the signals of cyclic unloading tensile failure were significantly more than those of cyclic loading. The AE signal characteristics studied in this article are of great significance for predicting coal power disasters.

Abstract Overall response rates in advanced Non-Small Cell Lung Cancer (NSCLC) remains low. Thus, novel molecular targets, tailored drugs and/or drug combinations are needed. Casein Kinase-2 (CK2) is a constitutively active and frequently over-expressed enzyme which fosters tumor survival, proliferation and metastasis. By using a clinical-grade and Cell Penetrating Peptide-based inhibitor coined as CIGB-300, we explore the anti-neoplastic effects caused by interruption of CK2 signaling in lung cancer cells lacking EGFR, ALK and ROS mutations. CIGB-300 penetrated and impaired viability and proliferation of Lung Adenocarcinoma (LUAD) (A549, NCI-H522) and Lung Squamous Carcinoma (LUSC) (NCI-H226 and SK-MES-1) cells in a dose-response manner. The differential activity could not be explained by overall peptide uptake or its subcellular distribution, as evidenced by flow cytometry and confocal microscopy. Upon internalization, CIGB-300 interacted with CK2 catalytic subunits (ɑ1/ɑ2) and CK2 substrates, thus impairing phosphorylation of enzyme substrates (CDC37s13, NPM1s125) and downstream proteins (RPS6s325/326). CK2 inhibition induced an early Reactive Oxygen Species (ROS) and mitochondrial membrane depolarization, which predates lung cancer cell death. Finally, intravenous injection of CIGB-300 in a cell line-based xenograft corroborated CIGB-300’s anti-tumor effects and suggested concurrent in situ reductions of CSNK2ɑ subunit and downstream RPS6s235/236 phosphorylation. Overall, CIGB-300 therapeutic hypothesis and antineoplastic effects demonstrated herein, further support the evaluation of this clinical-grade CK2 inhibitor in advanced NSCLC with limited therapeutic options.

Abstract Sediment dredging and aeration are used as important technical measures to remediate internal loading of sediment in polluted rivers. However, previous studies have overlooked the impact of dredging and aeration on Greenhouse gases (GHGs) emission. We established three aeration rate(six different aeration intervals), one dredging treatment to investigate the effect of aeration and dredging on pollutant removals and CO2, CH4 and N2O emissions. The results indicated the pollutants and GHGs at 2.4, 3.4, 4.4 L min−1 aeration rates reached collaborative emission reduction after more than 3 h or within 1.5 h. Meanwhile, the GHGs fluxes after aeration decreased with the increasing aeration rate, with the mean CO2, CH4 and N2O fluxes of 69.74, 0.16, 7.53 mg m−2 h−1 and 33.64, 0.09, 4.17 mg m−2 h−1 before and after aeration, respectively. With respect to dredging, the pollutants and N2O reached synergic effects between reduction of pollution and carbon emissions after 1 h dredging. Specifically, the CO2 and CH4 emissions after dredging was lower than those of before dredging, but the N2O emissions was higher than those of before dredging. In addition, our analysis revealed that the dissolved oxygen (DO), oxidation-reduction potential (ORP), available potassium (AK) and ammoniacal nitrogen (NH4 +-N) in the sediment influenced GHGs fluxes at the water-air interface in the aeration. Our study indicated moderate aeration and dredging can achieve the synergistic effect in reducing pollution and carbon emissions.

Abstract Older adults’ functional and intrinsic abilities may decline with increasing age. The positive effects of comprehensive community-based rehabilitation services to maintain physical, mental, and social function are essential. Nevertheless, few tools are available to assess the community-based rehabilitation needs of older adults. Therefore, we aimed to construct a list for the comprehensive evaluation of community-based rehabilitation needs of older adults. The International Classification of Functioning, Disability, and Health (ICF) was used to construct a first draft of the assessment list. From September to November 2023, 18 experts from five provinces and nine tertiary hospitals and institutions of higher education in China participated in this Delphi study. The older adult community-based rehabilitation needs evaluation list included six dimensions and 29 items. The weights of the six dimensions, from high to low, included mental function rehabilitation need (0.30), body function rehabilitation need (0.24), social participation need (0.18), individual activity rehabilitation need (0.14), environmental rehabilitation need (0.09) and rehabilitation information need (0.05). Using the Delphi method, an assessment list of older adult community-based rehabilitation needs based on ICF was developed. Future work should evaluate the list’s reliability and validity and its application in managing community-based rehabilitation for older adults.

Abstract Objectives MicroRNAs are considered as a class of potential biomarkers for HF. This study aimed to retrospectively evaluate the diagnostic and prognostic value of microRNA423-5p in patients with HF. Methods The observational group comprised 98 patients diagnosed with HF due to coronary atherosclerotic heart disease (n = 45), hypertension (n = 26), or cardiac valve insufficiency (n = 27). Conversely, the control group consisted of 30 healthy volunteers without any history of HF. These patients were further classified into heart function class II (n = 33), class III (n = 32), and class IV (n = 33) according to the NYHA classification. Of these patients, 33 were diagnosed with HF with mid-range ejection fraction (HFmrEF) and the remaining 65 with HF with reduced ejection fraction (HFrEF). The diagnostic and prognostic significance of microRNA423-5p in patients with HF was assessed through laboratory parameter assessments (microRNA423-5p and B-type natriuretic peptide test, BNP), cardiac ultrasound evaluations (left ventricular ejection fraction, LVEF), and subsequent follow-up assessments. Results In this study, we found that patients with HF exhibited notably elevated levels of microRNA423-5p and BNP, as well as significantly lower LVEF values. A significant positive correlation between microRNA423-5p and BNP indicators was validated. In addition, our study also revealed an elevation in the level of microRNA423-5p correlating with the progression of the HF. The combined evaluation of LEVF, BNP, and microRNA423-5p demonstrated superior diagnostic efficacy in comparison to the solitary use of BNP. Conclusions Elevated levels of microRNA423-5p in the serum of patients with HF suggest its potential utility as a novel biomarker for both the diagnosis and prognosis of this condition.

Abstract Background The triglyceride–glucose (TyG) index has demonstrated correlations with adverse clinical outcomes in patients with ischaemic stroke, coronary heart disease and cardiac failure. However, its association with overall mortality in individuals concurrently experiencing heart failure (HF) and chronic kidney disease (CKD) remains inadequately explored. Methods Utilizing the Medical Information Mart for Intensive Care IV (Version 2.2) repository, subjects underwent quartile stratification based on the TyG index. The primary endpoint was all‐cause mortality during hospitalization. Cox proportional hazard models were employed to examine the correlation between TyG and all‐cause mortality in HF patients with CKD. Evaluation involved Kaplan–Meier (KM) analysis and restricted cubic splines (RCSs) to compare mortality rates during hospitalization and 1 year after admission across cohorts with varying TyG index levels. Results A cohort of 1537 HF and CKD patients participated. Cox regression analysis revealed elevated TyG levels as an independent risk factor for both in‐hospital and 1 year mortality. RCS analysis indicated a rising, non‐linear association between TyG levels and all‐cause mortality (P value for non‐linear

For gastrointestinal anastomosis, metallic biodegradable staples have a broad application potential. However, both magnesium and zinc alloys have relatively low strength to withstand the repeated peristalsis of the gastrointestinal tract. In this study, we developed a novel kind of biodegradable high-nitrogen iron (HN–Fe) alloy wires (0.23 mm), which were fabricated into the staples. The tensile results showed that the ultimate tensile strength and elongation of HN–Fe wires were 1023.2 MPa and 51.0 %, respectively, which was much higher than those of other biodegradable wires. The degradation rate in vitro of HN–Fe wires was slightly higher than that of pure Fe wires. After 28 days of immersion, the tensile strength of HN–Fe wires remained not less than 240 MPa, meeting the clinical requirements. Furthermore, sixteen rabbits were enrolled to conduct a comparison experiment using HN–Fe and clinical Ti staples for gastroanastomosis. After 6 months of implantation, a homogeneous degradation product layer on HN–Fe staples was observed and no fracture occurred. The degradation rate of HN–Fe staples in vivo was significantly higher than that in vitro, and they were expected to be completely degraded in 2 years. Meanwhile, both benign cutting and closure performance of HN–Fe staples ensured that all the animals did not experience hemorrhage and anastomotic fistula during the observation. The anastomosis site healed without histopathological change, inflammatory reaction and abnormal blood routine and biochemistry, demonstrating good biocompatibility of HN–Fe staples. Thereby, the favorable performance makes the HN–Fe staples developed in this work a promising candidate for gastrointestinal anastomosis.

Abstract Background BCR-ABL is a constitutively active tyrosine kinase that stimulates multiple downstream signaling pathways to promote the survival and proliferation of chronic myeloid leukemia (CML) cells. The clinical application of specific BCR-ABL tyrosine kinase inhibitors (TKIs) has led to significantly improved prognosis and overall survival in CML patients compared to previous treatment regimens. However, direct targeting of BCR-ABL does not eradicate CML cells expressing T315I-mutated BCR-ABL. Our previous study revealed that inhibiting CREB binding protein (CBP) is efficacious in activating β-catenin/p300 signaling, promoting cell differentiation and inducing p53/p21-dependent senescence regardless of BCR-ABL mutation status. We hypothesize that the specific inhibition of CBP may represent a novel strategy to promote β-catenin/p300-mediated differentiation and suppress cancer cell proliferation for treating CML patients. Methods The anticancer efficacy of PBA2, a novel CBP inhibitor, in CML cells expressing wild-type or T315I-mutated BCR-ABL was investigated in vitro and in vivo. Cell differentiation was determined by the nitroblue tetrazolium (NBT) reduction assay. The extent of cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-Gal) activity. Cytotoxicity was measured by MTS assay. RNA interference was performed to evaluate the cell proliferation effects of CBP knockdown. The interaction of β-catenin and CBP/p300 was examined by co-immunoprecipitation assay. Results PBA2 exhibited significantly higher anticancer effects than imatinib in CML cells harboring either wild-type or T315I-mutated BCR-ABL both in vitro and in vivo. Mechanistically, PBA2 reduced CBP expression and promoted β-catenin-p300 interaction to induce cell differentiation and senescence. Conclusion Our data supported the rational treatment of CML by inhibiting the β-catenin/CBP pathway regardless of BCR-ABL mutation status.

Taxonomy plays a central role in understanding the diversity of life, translating the products of biological exploration and discovery specimens and observations into systems of names that settle a “classification home” to taxa. Up to this point, studies on the taxonomy and phylogeny of the basidiomycetous genus Tomentella stemmed mainly from the temperate to boreal zones of the North Hemisphere, but were scarce in tropical Asia. In this study, four new species, viz. Tomentella olivaceobasidiosa, T. velutina, T. wumenshanensis and T. yunnanensis from China, are described and illustrated based on the morphological characteristics and molecular phylogenetic analyses, in which the sequences of ITS+nLSU+mtSSU+RPB2 genes were used for the phylogenetic analyses using Maximum Likelihood, Maximum Parsimony and Bayesian Inference methods. All the new species can be well recognised by their macroscopical and anatomical characteristics. The four new species, closely related taxa in the phylogenetic tree and morphologically similar species are discussed.

Abstract Resistive memory devices feature drastic conductance change and fast switching dynamics. Particularly, nonvolatile bipolar switching events (set and reset) can be regarded as a unique nonlinear activation function characteristic of a hysteretic loop. Upon simultaneous activation of multiple rows in a crosspoint array, state change of one device may contribute to the conditional switching of others, suggesting an interactive network existing in the circuit. Here, we prove that a passive resistive switching circuit is essentially an attractor network, where the binary memory devices are artificial neurons while the pairwise voltage differences define an anti-symmetric weight matrix. An energy function is successfully constructed for this network, showing that every switching in the circuit would decrease the energy. Due to the nonvolatile hysteretic function, the energy change for bit flip in this network is thresholded, which is different from the classic Hopfield network. It allows more stable states stored in the circuit, thus representing a highly compact and efficient solution for associative memory. Network dynamics (towards stable states) and their modulations by external voltages have been demonstrated in experiment by 3-neuron and 4-neuron circuits.

Abstract Activin A and hepatic stellate cells (HSCs) are involved in tissue repair and fibrosis in liver injury. This study investigated the impact of activin A on HSC activation and migration. A microfluidic D4-chip was used for examining the cell migration of mouse hepatic stellate cell line MHSteC. The analysis of differentially expressed genes revealed that activin βA (Inhba), activin receptor type 1A (Acvr1a) and type 2A (Acvr2a) mRNAs were more significantly expressed in human HSCs than in the hepatocytes. Moreover, activin A promoted MHSteC proliferation and induced MHSteC migration. Furthermore, the MHSteCs treated with activin A exhibited increased levels of migration-related proteins, N-cadherin, Vimentin, α-SMA, MMP2 and MMP9, but a decreased level of E-cadherin. Additionally, activin A treatment significantly increased the p-Smad3 levels and p-Smad3/Smad3 ratio in the MHSteCs, and the Smad3 inhibitor SIS3 attenuated activin A-induced MHSteC proliferation and migration. Simultaneously, activin A increased the calcium levels in the MHSteCs, and the migratory effects of activin A on MHSteCs were weakened by the intracellular calcium ion-chelating agent BAPTA-AM. These data indicate that activin A can promote MHSteC activation and migration through the canonical Smad3 signaling and calcium signaling.

Abstract Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength (Zn-Prot M) can alleviate heat stress (HS)-induced intestinal barrier function damage of broilers. A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers. Under high temperature (HT), a 1 (Control, HT-CON) + 2 (Zn source) × 2 (added Zn level) factorial arrangement of treatments was used. The 2 added Zn sources were Zn-Prot M and Zn sulfate (ZnS), and the 2 added Zn levels were 30 and 60 mg/kg. Under normal temperature (NT), a CON group (NT-CON) and pair-fed group (NT-PF) were included. Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1, occludin, junctional adhesion molecule-A (JAMA), zonula occludens-1 (ZO-1) and zinc finger protein A20 (A20) in the jejunum, and HS also remarkably increased serum fluorescein isothiocyanate dextran (FITC-D), endotoxin and interleukin (IL)-1β contents, serum diamine oxidase (DAO) and matrix metalloproteinase (MMP)-2 activities, nuclear factor kappa-B (NF-κB) p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg/kg, significantly decreased serum FITC-D, endotoxin and IL-1β contents, serum DAO and MMP-2 activities, NF-κB p65 mRNA expression level, and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers, and notably promoted mRNA and protein expression levels of claudin-1, ZO-1 and A20. Conclusions Our results suggest that dietary Zn, especially 60 mg Zn/kg as Zn-Prot M, can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.

In the current study, the corrosion behavior of HSLA-65 steel was investigated in a simulated marine environment inoculated with P. aeruginosa. In the electrochemical measurements, the negative shift in OCP, lower values of corrosion potential, pitting potential, and increased corrosion current density of the HSLA-65 steel in the biotic medium signified its low corrosion resistance in the presence of P. aeruginosa. The observation of the surface morphology revealed biofilm formation on the steel surface in the P. aeruginosa-inoculated culture medium, which significantly accelerated the pitting corrosion of the steel. The pit observed on the steel surface in the biotic medium was about 3.9 times deeper than in the sterile medium. In addition, the weight loss of the steel in the biotic medium was about 2.4 times higher compared to that in the sterile medium. These findings suggest that the P. aeruginosa biofilm significantly accelerated the corrosion of HSLA-65 steel in the simulated marine environment.

Abstract We derive the exact solutions for electrically charged black holes both in the absence and presence of a cosmological constant in the gravitational theory with Lorentz violation induced by a background Kalb–Ramond (KR) field. The corresponding thermodynamic properties are investigated. It is found that the standard first law of thermodynamics and the Smarr formula remain valid for the charged KR black holes. Nevertheless, the Lorentz-violating effect influences their ranges of local thermodynamic stability and the first- and second-order phase transition points. Furthermore, to examine the impact of Lorentz violation on the motion of test particles in the spacetime, we analyze the shadow and the innermost stable circular orbit (ISCO) of these black holes. Our results reveal that both the shadow and ISCO radii exhibit a high sensitivity to the Lorentz-violating parameter $$\ell $$ ℓ , with a decrease observed as $$\ell $$ ℓ increases.

Abstract The low ionic conductivity of composite solid-state electrolytes due to the lack of free Li-ions and Li dendrite growth induced by the low transference number seriously hinder their application. Herein, we find that the giant dielectric ceramic of Li0.3Ti0.02Ni0.68O (LTNO) with ultra-high dielectric constant can greatly promote the dissociation of Li salt to generate abundant movable Li-ions and realize a high room-temperature ionic conductivity (4.09 × 10–4 S cm−1) as well as a low activation energy (0.16 eV). The oxygen vacancies on the surface of LTNO can effectively immobilize the anions to achieve a high Li transference number (0.61). Furthermore, the enhanced dielectric properties of the composite electrolyte induce homogenous Li plating/stripping to suppress the growth of Li dendrites. As a result, the Li||Li symmetric cells exhibit long lifespan of 2400 h and 1150 h at 0.1 mA cm−2 and 0.2 mA cm−2, respectively. The Li||LiNi0.8Co0.1Mn0.1O2 solid-state full cells show a high capacity retention of 83% after 430 cycles at 2C. This work highlights the critical role of high dielectric property and oxygen defects of fillers in composite solid-state electrolytes, and provides a demonstration for the application of giant dielectric materials in solid-state Li metal batteries.

1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] could promote phosphorus (P) absorption in the duodenum of broilers. The vitamin D receptor (VDR) mediates the action of 1,25-(OH)2D3. However, it remains unknown whether and how VDR is involved in promoting P absorption in the duodenum of broilers by 1,25-(OH)2D3. The objective of the current study was to investigate the effect of added 1,25-(OH)2D3 levels on P absorption, mRNA or protein expression levels of VDR, retinoid X receptor (RXR), type IIb sodium-phosphate cotransporter (NaPi-IIb), inorganic phosphate transporter (PiT) 1 and PiT-2, and the enrichments of VDR bound to DNA promoters of the above P transporters in the ligated duodenal loops of Arbor Acres male broilers. The duodenal loops were perfused with solutions (pH = 6.0) containing 0 (control), 12.5, or 25.0 ng/L of 1,25-(OH)2D3 for up to 40 min. The results indicated that the addition of either 12.5 or 25.0 ng/L 1,25-(OH)2D3 to the perfusates increased (P < 0.04) P absorption percentage and rate, as well as the mRNA expression levels of VDR, RXR, NaPi-IIb, and PiT-2, alongside protein expression levels of VDR, NaPi-IIb, and PiT-2, whereas it did not affect (P > 0.10) PiT-1 mRNA and protein expression levels. Moreover, 1,25-(OH)2D3 administration increased (P < 0.01) the enrichments of VDR bound to NaPi-IIb and PiT-2 DNA promoter regions in the ligated duodenal loops of broilers, which were in line with their mRNA expression levels. These findings suggest that 1,25-(OH)2D3 increased P absorption possibly through VDR-mediated transactivation of NaPi-IIb and PiT-2 genes in the duodenum of Arbor Acres male broilers.

The quality of Chinese herbal medicines is the key to the quality of traditional Chinese medicine. The processing of Chinese herbal medicines is an important part of the production and quality formation of medicinal materials. Traditional processing methods have low productivity and cannot guarantee the quality of Chinese herbal medicines. Among various non-thermal processing methods, ultrasonic technology has been proved to be a very valuable green processing technology. This paper will discuss the application of ultrasonic technology in the production and processing of Chinese herbal medicines in recent years, including the extraction, cleaning, drying and sterilization of effective components of Chinese herbal medicines. This review summarizes its principle, characteristics and application progress in recent years, and discusses its existing problems. The effects of ultrasound on the chemical structure and biological activity of bioactive compounds extracted from Chinese herbal medicines are mainly introduced. In addition, this paper discusses the effects of different ultrasonic conditions such as frequency, power, time and temperature on the chemical properties and processing of Chinese herbal medicines. In general, the use of ultrasound in the production and processing of Chinese herbal medicines has great application potential.

Dragon’s blood (Resina Draconis) is the red resin of Dracaena spp, which has a variety of biological activities and pharmacological effects, including anti-thrombotic, anti-inflammatory, anti-bacterial, analgesic, anti-oxidant, anti-tumor, and immunosuppressive. In China, the main source of dragon’s blood is Dranaena Cochinchinensis (Lour.) S.C.Chen. A wide array of studies have speculated that the dragon’s blood derived from Dranaena Cochinchinensis (Lour.) S.C.Chen possesses cardiovascular protective effects. It has been reported that Chinese dragon’s blood can potentially alleviate and treat conditions such as coronary heart disease, myocardial infarction, and myocardial ischemia–reperfusion through its anti-inflammatory and antioxidant properties, which have not been systematically stated in previous reviews. Moreover, the precise underlying pharmacological mechanisms through which the Chinese dragon’s blood exhibits cardioprotective effects are not fully understood. Therefore, this article discusses the pharmacological action and biomolecular mechanism of dragon’s blood from Dranaena Cochinchinensis (Lour.) S.C.Chen and how it prevents and protects against cardiovascular diseases. The review article concludes with prospects for further application of dragon’s blood in respect to cardiovascular diseases.

Childhood asthma, a common chronic childhood disease, leads to high mortality and morbidity in the world. Airway smooth muscle cells (ASMCs) is a group of multifunctional cells that has been found to be correlated with the pathogenesis of asthma. Astragaloside IV (AS-IV) is a compound extracted from Astragalus membranaceus, which has the anti-asthmatic effect. However, the role of molecular mechanisms regulated by AS-IV in the biological processes of ASMCs in asthma remains unclear. Our current study aims to investigate the downstream molecular mechanism of AS-IV in modulating the aberrant proliferation and pyroptosis of ASMCs in asthma. At first, we determined that the viability of ASMCs could be efficiently suppressed by AS-IV treatment (200 μM). Moreover, AS-IV promoted the pyroptosis and suppressed PDGF-BB-induced aberrant proliferation. Through mechanism investigation, we confirmed that AS-IV could suppress high mobility group box 1 (HMGB1) expression and prevent it from entering the cytoplasm. Subsequently, AS-IV blocked the interaction between HMGB1 and advanced glycosylation end product-specific receptor (RAGE) to inactivate NF-κB pathway. Finally, in vivo experiments demonstrated that AS-IV treatment can alleviate the lung inflammation in asthma mice. Collectively, AS-IV alleviates asthma and suppresses the pyroptosis of AMSCs through blocking HMGB1/RAGE axis to inactivate NF-κB pathway.

Extra-thick key strata (ETKS) are a key factor causing coal bursts. In this study, field monitoring, physical and numerical modelling, and theoretical analysis were comprehensively adopted to investigate the effect of ETKS on the static and dynamic stress and its impact on coal bursts. Firstly, the coal bursts and the stability of ETKS were investigated. The roof strata structure and the mining-induced stress in a large scale panel under ETKS were analyzed. Then, the coal burst mechanism under ETKS is discussed. The results show that when the panel reaches the 4th and 5th longwall faces, the inferior ETKS and the main ETKS break, respectively, and large-scale cantilever-articulated structures involving the ETKS are formed. This moment, the overburden load is transferred downwards massively, and the coal seam becomes overstressed and accumulates massive elastic energy. Meanwhile, the collaborative collapse of multiple strata in the large cantilever-articulated structures causes the sudden release of elastic energy and high-energy seismicity, which exerts strong dynamic disturbances on the overstressed coal mass and leads to coal burst. Finally, strategies for coal burst control under ETKS including deep-hole pre-splitting blasting and panel size optimization are proposed and validated.

During chronic infection or tumorigenesis, persistent antigen stimulation contributes to the exhaustion of CD8+ T cells. Nevertheless, exhausted CD8+ T (TEX) cells still preserve certain effector function, and maintaining a reservoir of exhausted cells is of vital importance for virus elimination and tumor eradiation. Despite considerable work interrogating the rejuvenation of TEX cells, mechanisms underpinning the clonal deletion of TEX cells remain largely unexplored over the past decade. In this study, we employed mouse models of LCMV infection to demonstrate that excessive accumulation of lipid peroxidation rendered virus-specific TEX cells to ferroptosis, which may correlate with enhanced mitochondria-derived oxidative stress and compromised activity of glutathione peroxidase 4 (GPX4). In addition, either incomplete or complete ablation of GPX4 resulted in exacerbated ferroptosis and aggravated shrunken population of virus-specific TEX cells. On the other hand, inhibiting ferroptosis via administration of a ferroptosis inhibitor or overexpression of GPX4 greatly rectified the cell loss of virus-specific TEX cells. Collectively, we disclosed ferroptosis as a crucial player in the clonal deletion of virus-specific TEX cells and stressed the intervention of ferroptosis as a promising approach to optimize the longevity of virus-specific TEX cells.

ObjectiveTo describe the trends in the incidence of hand, foot and mouth disease (HFMD) before, during, and after China’s Coronavirus Disease (COVID) control policies, and to interpret the influence on HFMD incidence at different control stages in Zhejiang Province.MethodsWe collected data on HFMD cases in Zhejiang between 2014 and 2023. We compared the constituent ratios of cases at different COVID control stages by sex, age, child groups, and pathogens and weekly seasonal indices to observe seasonal variations in the incidence of HFMD. An interrupted time-series segmented regression analysis was applied to estimate the influence on HFMD incidence at different control stages. Stratified and sensitivity analyses were conducted to validate the findings.ResultsA considerable proportion of cases occurred among children living separately. The proportions of children in kindergartens or nurseries and children aged 2–4 years were relatively low at the strict control stage compared to the other three stages. Enteroviruses other than enterovirus 71 and coxsackie virus A16 were the dominant HFMD pathogens, and the proportion showed an increasing trend. The usual spring–summer peak in HMFD incidence did not occur in 2020, and the periodicity of the biennial peak was disrupted for a year. The summer peak in 2023 was higher than that in the other years, and was delayed by 3 weeks. The trend changes in weekly HFMD cases during the strict control and regular control stages were − 15% (IRR: 0.85, 95% CI: 0.81–0.89) and 17% (IRR: 1.17, 95% CI: 1.12–1.23), respectively. However, the change was not statistically significant during the reopening stage (IRR: 1.41, 95% CI: 0.34–5.88). The expected number of cases increased by 1.12 times (95% CI: 243.17, 53.45%) during the reopening stage compared to what would have occurred if the zero-COVID policy had continued in 2023.ConclusionNon-pharmaceutical interventions (NPIs) for COVID-19 control can mitigate HFMD. However, after the dynamic zero-COVID policy ended, the HFMD incidence returned to historical levels. Strict NPIs such as traffic restrictions and kindergarten closures cannot be sustained long-term. NPIs such as improving personal hygiene for routine prevention are highly recommended.

Acute myeloid leukemia (AML), a malignant disorder of the hematopoietic system, arises from leukemic stem cells (LSCs) and is the most prevalent form of blood cancer in adults. This study aimed to evaluate the therapeutic potential of polydatin (PD) in AML through ex vivo and in vivo studies, respectively. This study was prompted by PD’s novel role in enhancing tumor apoptosis and modulating autophagy. In vitro studies were conducted using the PD-responsive AML cell line KASUMI-1 and found that PD was able to suppress cell proliferation and induce apoptosis by regulating the autophagy pathway. Subsequently, molecular docking was employed to predict the interaction between PD and Autophagy-related protein 5 (ATG5), a key regulator in the autophagy pathway. It was observed that PD inhibited the ubiquitination of ATG5 and enhanced its protein stability, leading to an increase in ATG5 protein levels and subsequent activation of the autophagy pathway (see in Abstract Graphed). The effectiveness and safety of PD in treating AML were confirmed through in vivo experiments using a mouse transplant tumor model, yielding definitive results. Collectively, these results suggest that PD is a promising candidate for the early therapeutic intervention of AML, with a strong potential for clinical application.

Background and purposeInfantile cerebellar retinal degeneration (ICRD) (OMIM #614559) is a rare autosomal recessive inherited disease associated with mutations in the aconitase 2 (ACO2) gene. We report a Chinese girl with novel compound heterozygous variants in ACO2, who presented at 7 months of age with psychomotor retardation, truncal hypotonia, and ophthalmologic abnormalities. This study aims to investigate the potential molecular mechanisms underlying ACO2 deficiency-induced neuropathy.MethodsWhole exome sequencing was performed on family members to screen for potential pathogenic mutations, followed by Sanger sequencing for validation. Mitochondrial aconitase activity and mitochondrial DNA (mtDNA) copy number were measured using an aconitase activity detection kit and quantitative PCR, respectively. Transcriptome expression profiles from patient cells, and cerebellar and retinal organoids retrieved from the GEO database were integrated. Functional enrichment analysis and protein-protein interaction networks were used to identify key molecules, and their expression levels were validated using Western blot analysis.ResultsGenetic testing revealed novel compound heterozygous variations in the proband's ACO2 gene (NM:001098), including c.854A>G (p.Asn285Ser) and c.1183C>T (p.Arg395Cys). Predictive analysis of the tertiary structure of the ACO2 protein suggests that both p.Asn285Ser and p.Arg395Cys affect the binding ability of ACO2 to ligands. The mitochondrial aconitase activity and mtDNA copy number in the proband's leukocytes were significantly reduced. Transcriptomic data analysis identified 80 key candidate genes involved in ACO2-related neuropathy. Among these, LRP8 and ANK3, whose gene expression levels were significantly positively correlated with ACO2, were further validated by Western blot analysis.ConclusionsThis study expands the spectrum of pathogenic ACO2 variants, elucidates the potential molecular mechanisms underlying ACO2-related neuropathy, provides in-depth support for the pathogenicity of ACO2 genetic variations, and offers new insights into the pathogenesis of ICRD.

The Japanese encephalitis virus (JEV), a zoonotic flavivirus, is Asia’s primary cause of viral encephalitis. JEV induces apoptosis in a variety of cells; however, the precise mechanisms underlying this apoptosis resulting from JEV infection remain to be elucidated. Our previous studies showed that the proapoptosis gene BAX may have a role in JEV proliferation. In this study, we constructed a PK-15 cell line (BAX.KO) with a knockout of the BAX gene using CRISPR/Cas9. The knockout of the BAX gene effectively inhibited the proliferation of JEV, resulting in a 39.9% decrease in viral protein levels, while BAX overexpression produced the opposite effect. We confirmed that JEV induces apoptosis of PK-15 using 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V-FITC/PI staining. Furthermore, we found that the phosphorylation of P53 and the expression levels of BAX, NOXA, PUMA, and cleaved-caspase-3/9 were significantly upregulated after JEV infection. Moreover, we found that JEV infection not only caused mitochondrial damage, the release of mitochondrial cytochrome C (Cyt C), and the downregulation of the apoptosis-inhibiting protein BCL-2 but also reduced the mitochondrial membrane potential (MOMP) and the accumulation of intracellular reactive oxygen species (ROS). These factors collectively encourage the activation of the mitochondrial apoptosis pathway. In contrast, BAX gene knockout significantly reduces the apoptotic changes caused by JEV infection. Treatment with the caspase3 inhibitor attenuated JEV-induced viral proliferation and release, leading to a decrease in viral protein levels of 46% in PK-15 cells and 30% in BAX.KO cells. In conclusion, this study clarified the molecular mechanisms of JEV-induced apoptosis and provided a theoretical basis for revealing the pathogenic mechanisms of JEV infection.

Intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) syndrome elicited neuron injury (especially in the hippocampus and cortex), contributing to cognitive dysfunction. This study investigated the effects and clarified the mechanisms of ETS domain-containing protein Elk-4 (ELK4) on the cognitive function and neuroinflammation of mice with IH. Mouse microglia BV2 cells were induced with IH by exposure to fluctuating O2 concentrations (alternating from 5 % to 21 % every 30 min), and mice with OSA were developed and subjected to lentivirus-mediated gene intervention. ELK4 expression was significantly reduced in IH-induced microglia and brain tissues of mice with OSA. Overexpression of ELK4 attenuated oxidative stress, decreased the pro-inflammatory factors IL-1β, IL-6, and TNF-α, and increased the level of the anti-inflammatory factors IL-10 and TGF-β1, as well as the neuroprotective factor BDNF. ELK4 promoted the transcription of fibronectin type III domain-containing protein 5 (FNDC5) by binding to the promoter of FNDC5. Knockdown of FNDC5 in IH-induced microglia and animals reversed the protective effects of ELK4 on OSA-associated neuroinflammation and cognitive dysfunction. Overall, the results demonstrated that ELK4 overexpression repressed microglial activation by inducing the transcription of FNDC5, thus attenuating neuroinflammation and cognitive dysfunction induced by OSA.

Abstract Background This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. Methods By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. Results The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P

Laser powder bed fusion (LPBF) technology enables personalized customization of medical implants. However, the clinical titanium alloy is biologically inert and can't address bacterial infections. It has been proved that Copper (Cu) -bearing titanium alloys exhibit excellent antibacterial ability and potentials for clinical application. However, it still unclear that the effect of Cu content on the comprehensive properties of LPBF-produced titanium alloy which usually has high strength but poor ductility and corrosion resistance caused by its α′ martensite. This study systematically investigates the effects of Cu content (x = 2, 5, 8 wt%) on the microstructure, mechanical properties, corrosion resistance, antibacterial properties, and cytrocompatibility of the LPBF-produced Ti-xCu alloys. These results prove that the LPBF produced Ti–5Cu alloy possesses the optimal comprehensive performance and has promising clinical application prospects as implant materials.

In order to investigate the influence of gradual stress relieving treatment on the microstructure, texture evolution, grain structure, and misorientation distribution of the hot-rolled Ti6Al4V–5Cu (α+β) alloy deformed in various thickness reduction ratios (TRR's) of 15%, 58%, and 73% to maintain the burger orientation relationship (BOR), different stress reliving treatment was specially designed for relieving the residual stresses occurred due to the hot deformation process. Using IPF maps, the majority of the α grains, specifically the elongated ones were found nearly at 45 ° with respect to the rolling and transverse direction. The study also show that the heat treatment schedule on the 58% deformed alloy significantly promote the transformation of β to α phase and a special microstructure with an equiaxed grains is produced. The local misorientation angle distribution due to stress reliving treatment has also discussed. Using EBSD analysis, the alloy processed under highest TRR's (i.e., 73%) and subsequent stress relieving treatment could result a serious internal crystalline instability with various degree of element diffusion rate, which promote a severe and ease of alloy coarsening. Thus, coarsening encourage the formation of grains with the highest softening potential, comparatively. It is obvious that the stress-relived treatment does not result a change in microstructure. However the internal residual stresses on the hot deformation were relieved, the texture intensity had increased quietly. A significant textural behavior could be achieved on the 73% hot-rolled alloys by the stress-relieving process to align the α/β fiber texture interface in parallel coincidence to maintain the BOR.

Abstract This study investigates the stability of an artificial dam used in an underground reservoir in a coal mine under periodic weighting imposed by overlying rock strata. For this purpose, cyclic loading and unloading tests with different stress amplitudes were designed. Differences in the mechanical performance of the artificial dam with and without overlying strata were analyzed using a uniaxial compression test. The mechanical properties of the structure under constant-amplitude cyclic loading and unloading were characterized. Further, the law of influence of stress amplitude on stability was discussed. A formula for predicting the mechanical performance of the artificial dam with its overlying rocks (hereafter referred to as the complex) was finally derived and was suitable for clarifying the law of damage in the complex under cyclic loading and unloading. The results showed that the complex had changed the internal structure of rocks. The strength and deformation of the complex were intermediate to that of either single structure. All three underwent brittle failure. During the constant-amplitude loading and unloading tests, the hysteresis loop could be divided into three phases, namely, sparse, dense, and sparse again, with a shift in the turning point in rock deformation memory effect. As the stress amplitude increased during the test, the damping ratio of the specimens decreased, and the area of the hysteresis loop increased non-linearly. The dynamic elastic modulus decreased first and then increased. The confidence interval for the formula fitted based on the test results was above 97%. Damage to the complex caused by constant-amplitude loading and unloading could be divided into three stages. An increase in peak stress served as a catalyst for the evolution of small cracks within the specimens into median and large cracks, thereby accelerating the damage process.

Huainan mining area is a typical high-gas area, with broken soft coal seam, low permeability, high gas content, and difficulty in extraction. In order to probe into the technical feasibility and gas control effect of the horizontal well for segmental hydraulic fracture in roof of coal seam in mining area, a three-dimensional in-situ stress test of coal seam was carried out using the stress relief method based on the analysis of the characteristics of the 13-1 coal reservoir, which was the main coal seam in the mining area. The results shown that, the three-dimensional stress field was mainly σh,max > σv > σh,min, which had sufficient conditions for the implementation of horizontal well with segmental hydraulic fracture in roof of coal seam. MFrac Suite software was used to simulate the fracture parameters of horizontal section at 1, 3 and 5 m from the coal seam. The maximum half-length of the fracture was 107.33 m and the minimum was 89.47 m, which was ideal for fracturing, indicating that the horizontal well with segmental hydraulic fracture had better geological adaptability and feasibility in Huainan mining area. Taking the CBM01 well, a horizontal well with L-type roof segmental fracturing in the 13-1 coal seam of Panyi coal mine, as the research object, the effect of gas control and management was comprehensively analyzed by means of borehole detection and numerical simulation. The results shown that, CBM01 well significantly reduced the gas pressure and gas content of coal seam after 415 d of extraction. The gas pressure at 50 and 65 m from the horizontal well decreased from 6.4 MPa to 2.6 and 2.7 MPa, respectively, by more than 55%. The gas content decreased from 13.5 m3/t to a maximum of 9.11 m3/t, a minimum of 6.92 m3/t, an average of 7.92 m3/t in an area of about 15-20 m on each side of the horizontal section, and decreased to less than 8 m3/t within about 10 m. Finally, a numerical simulation method was used to predict the gas production effect of CBM 01 well extracting for 10 a and the effect with gas control. The cumulative gas production of gas well was about 272.08×104 m3 in 10 a, and the gas content in the range of about 150 m on one side of the horizontal section was reduced to less than 8 m3/t, and the pressure was reduced to less than 3 MPa. Comprehensive research results shown that the horizontal well technology of segmental hydraulic fracturing in roof of coal seam had greater advantage and application effect in gas control and management in Huainan mining area.

The construction of 14 large-scale coal bases and 89 demonstration bases for the comprehensive utilization of bulk solid waste in China marks that the utilization of bulk solid waste in mining areas has been incorporated into the national strategic development layout. The long-term high-intensity development and utilization of coal resources has caused the near depletion of shallow-buried coal seam resources in mining areas, and the large-scale solid waste accumulation and surface subsidence of coal power and chemical bases has become a problem restricting the green, low-carbon and high-quality development of mining areas. Co-operative utilization of bulk coal-based solid waste and green filling is an effective way to liberate the “three down and one up” pressed coal, extend the service life of mines, and realize the harmless, resourceful, and large-scale “three” utilization of solid waste. Based on the types and production of coal-based solid waste in Shanxi Province, the “East China Energy Granary” Anhui Lianghuai Base and Ningdong Energy and Chemical Base, it elaborates in detail the harmless disposal of coal-based solid waste through heavy metal adsorption and desorption and complexation passivation technology with coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials, listing the classification and application of coal-based solid waste, and the application of coal gangue, fly ash, furnace slag, gasification slag and desulphurization gypsum as the main materials. List the ways of resource utilization of coal-based solid waste classified and applied to low calorific value coal-based solid waste for power generation, preparation of building materials such as cement, bricks and tiles, etc. Comparatively analyze the ways of reclamation and backfilling of coal mining subsidence area and downhole filling and large-scale utilization of coal-based solid waste, highlighting the superiority of downhole filling of coal-based solid waste. Based on the deep coal resources of coal electrification bases, the theory and key technologies of green filling mining are proposed, including the synergistic technology of deep coal gangue source reduction and mining and filling, the technology of efficient preparation and deep underground transportation of filling materials, and the deep multi-field coupling mechanism of coal-based solid waste filling materials, and the technological principles and methods of the whole process of deep filling mining of multi-source coal-based solid waste from the source, process to the end are investigated to solve the technical problems of deep underground filling of mining areas. The technical problems of filling are solved. According to the geological conditions and filling purposes of Renjiazhuang Coal Mine in Ningdong Base, Huoerxinhe Coal Mine in Shanxi Province and Huaibei Mining Area, the key technologies of low-level filling by overdrilling, multi-separation layer stepped grouting under the conditions of atypical characteristics of key layers and synergistic utilization of coal-based solid wastes have been proposed, which comprehensively combine the advantages of disposal and utilization of solid wastes from mines, development and utilization of deep coal resources, control of subsidence of the ground surface, and ecological environment protection, and form a comprehensive plan for the disposal and utilization of bulk solid wastes from coal power and chemical bases. Coal power and chemical base bulk solid waste synergistic utilization and green mining mode, providing reference for high quality coal mining and low damage to the environment.

In order to study the consolidation bearing capacity of coal-based solid waste paste backfill in deep high ground temperature environment of coal mine, uniaxial compression and acoustic emission tests were used to test the strength and failure characteristics of paste backfill under different curing temperature conditions (20 ℃, 35 ℃ and 50 ℃) and ages (3 d, 7 d, 14 d and 28 d). The microstructure and mineral composition of the filling cement were measured by SEM, and the influence of curing temperature on the hydration reaction was revealed from the microscopic point of view. The results show that: with the increase of curing temperature, its influence on hydration reaction gradually changes from promotion to inhibition, and the 28 d compressive strength reaches the maximum at 35 ℃; acoustic emission events mainly occur in the compaction and failure stages. The increase of curing temperature promotes the activity of acoustic emission in advance, and the failure mode of filling body gradually changes from ductile failure to brittle failure; due to the thermal damage, high temperature curing accelerates the early hydration reaction rate of the filling body, and causes damage to the C-S-H and pore structure of the filling body in the later stage of curing, which has an adverse effect on the increase of its long-term strength.

Abstract Background Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study. Methods Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran’s Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability. Results Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003–1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096–2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results. Conclusion This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.

We conduct a detailed analysis of the full linear perturbations in the braneworld scenario within f(T) gravity. By decomposing the perturbations of the theory into the scalar, transverse vector, antisymmetric pseudotensor, and symmetric transverse-traceless tensor modes, we derive the quadratic action for each mode. The results indicate that there is a total of one scalar, one massless vector, and one tensor propagating degrees of freedom. Consequently, in comparison to general relativity, no additional degrees of freedom appear under the flat braneworld background in the linearized theory. For a thick brane model with f(T)=T+αT2, we find that it exhibits stability against linear perturbations.

Abstract Integration of solar cell and secondary battery cannot only promote solar energy application but also improve the electrochemical performance of battery. Lithium–sulfur battery (LSB) is an ideal candidate for photoassisted batteries owing to its high theoretical capacity. Unfortunately, the researches related the combination of solar energy and LSB are relatively lacking. Herein, a freestanding photoelectrode is developed for photoassisted lithium–sulfur battery (PALSB) by constructing a heterogeneous structured Au@N‐TiO2 on carbon cloths (Au@N‐TiO2/CC), which combines multiple advantages. The Au@N‐TiO2/CC photoelectrode can produce the photoelectrons to facilitate sulfur reduction during discharge process, while generating holes to accelerate sulfur evolution during charge process, improving the kinetics of electrochemical reactions. Meanwhile, Au@N–TiO2/CC can work as an electrocatalyst to promote the conversion of intermediate polysulfides during charge/discharge process, mitigating induced side reactions. Benefiting from the synergistic effect of electrocatalysis and photocatalysis, PALSB assembled with an Au@N‐TiO2/CC photoelectrode obtains ultrahigh specific capacity, excellent rate performance, and outstanding cycling performance. What is more, the Au@N‐TiO2/CC assembled PALSB can be directly charged under light illumination. This work not only expands the application of solar energy but also provides a new insight to develop advanced LSBs.

BackgroundChina is one of the main epidemic areas of scrub typhus, and Zhejiang Province, which is located in the coastal area of southeastern China, is considered a key region of scrub typhus. However, there may be significant bias in the number of reported cases of scrub typhus, to the extent that its epidemiological patterns are not clearly understood. The purpose of this study was to estimate the possible incidence of scrub typhus and to identify the main driving components affecting the occurrence of scrub typhus at the county level.MethodsData on patients with scrub typhus diagnosed at medical institutions between January 2016 and December 2023 were collected from the China Disease Control and Prevention Information System (CDCPIS). The kriging interpolation method was used to estimate the possible incidence of scrub typhus. Additionally, a multivariate time series model was applied to identify the main driving components affecting the occurrence of scrub typhus in different regions.ResultsFrom January 2016 to September 2023, 2,678 cases of scrub typhus were reported in Zhejiang Province, including 1 case of reported death, with an overall case fatality rate of 0.04%. The seasonal characteristics of scrub typhus in Zhejiang Province followed an annual single peak model, and the months of peak onset in different cities were different. The estimated area with case occurrence was relatively wider. There were 41 counties in Zhejiang Province with an annual reported case count of less than 1, while from the estimated annual incidence, the number of counties with less than 1 case decreased to 21. The average annual number of cases in most regions fluctuated between 0 and 15. The numbers of cases in the central urban area of Hangzhou city, Jiaxin city and Huzhou city did not exceed 5. The estimated random effect variance parameters σλ2, σϕ2, and σν2 were 0.48, 1.03 and 3.48, respectively. The endemic component values of the top 10 counties were Shuichang, Cangnan, Chun’an, Xinchang, Pingyang, Xianju, Longquan, Dongyang, Yueqing and Qingyuan. The spatiotemporal component values of the top 10 counties were Pujiang, Anji, Pan’an, Dongyang, Jinyun, Ninghai, Yongjia, Xiaoshan, Yinwu and Shengzhou. The autoregressive component values of the top 10 counties were Lin’an, Cangnan, Chun’an, Yiwu, Pujiang, Longquan, Xinchang, Luqiao, Sanmen and Fuyang.ConclusionThe estimated incidence was higher than the current reported number of cases, and the possible impact area of the epidemic was also wider than the areas with reported cases. The main driving factors of the scrub typhus epidemic in Zhejiang included endemic components such as natural factors, but there was significant heterogeneity in the composition of driving factors in different regions. Some regions were driven by spatiotemporal spread across regions, and the time autoregressive effect in individual regions could not be ignored. These results that monitoring of cases, vectors, and pathogens of scrub typhus should be strengthened. Furthermore, each region should take targeted prevention and control measures based on the main driving factors of the local epidemic to improve the accuracy of prevention and control.

Background: KIDINS220 encodes a transmembrane scaffold protein, kinase D-interacting substrate of 220 kDa, that regulates neurotrophin signaling. Variants in KIDINS220 have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome or prenatal fatal cerebral ventriculomegaly and arthrogryposis (VENARG). This study aimed to investigate the genotype-phenotype correlation of pathogenic KIDINS220 variants. Methods: We performed whole-exome sequencing on a patient with SINO syndrome and epilepsy. Identified pathogenic variants were confirmed using Sanger sequencing and evaluated with in silico tools. A comprehensive literature review was conducted to analyze the genetic and phenotypic data of both the newly diagnosed patient and previously reported cases with KIDINS220 variants. Results: We identified novel compound heterozygous variants in KIDINS220, c.1556C > T (p.Thr519Met) and c.2374C > T (p.Arg792*), in the patient. Our analysis revealed that biallelic loss-of-function variants in KIDINS220 are associated with VENARG or autosomal recessive SINO (AR-SINO), whereas carboxy-terminal truncated variants that escape nonsense-mediated mRNA decay and lack amino acid residues 1507–1529 are linked to autosomal dominant SINO (AD-SINO). Patients with AR-SINO exhibit more severe clinical features compared to those with AD-SINO. Conclusions: Our study expands the spectrum of KIDINS220 variants associated with AR-SINO and provides a valuable genotype-phenotype correlation for pathogenic KIDINS220 variants.

Objective: The present study aimed to explore the potential causal relationship between childhood asthma and chronic obstructive pulmonary disease (COPD) in European and East Asian populations with Mendelian randomization (MR) analysis. Methods: Based on summary data from genome-wide association studies, single nucleotide polymorphisms (SNPs) associated with childhood asthma were used as instrumental variables. The MR analysis employed the inverse variance weighting, MR-Egger regression and weighted median method to estimate the causal effect between childhood asthma and COPD in European and East Asian populations. Cochran's Q test, MR-PRESSO method and MR-Egger intercept were used to detect heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis applied to assess the effect of removing individual SNP on the estimate of causal association. Results: The MR analysis showed no genetic causal relationship between childhood asthma and COPD. The results of Cochran's Q test, MR-PRESSO and MR-Egger regression indicated the absence of heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis showed no significant difference in the statistical results after exclusion of single SNPs. Conclusions: The MR analysis revealed that there is no causal relationship between childhood asthma and COPD at the genetic level in both European and East Asian populations. Additionally, due to the presence of shared confounding factors and pathogenic genes, further research is needed to comprehensively assess the relationship between childhood asthma and COPD.

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation with ultrasound, these proteins trigger a cascade of cellular activities and functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision and safety in disease treatment. This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, and beyond. Although current literature predominantly emphasizes ultrasonic neuromodulation, this review offers a comprehensive exploration of sonogenetics. We discuss ultrasound properties, the specific ultrasound-sensitive proteins employed in sonogenetics, and the technique's potential in managing conditions such as neurological disorders, cancer, and ophthalmic diseases, and in stem cell therapies. Our objective is to stimulate fresh perspectives for further research in this promising field.

BackgroundThe aim of the present study was to investigate the intrinsic relationship between cultural values and social network index among college students. In addition, the present study explored the mediating role of self-monitoring in the relationship between horizontal collectivism cultural values and social network index, as well as the moderating role of self-efficacy, to provide a theoretical approach based on the intrinsic mechanism for college students to establish a good social network.MethodsA simple random cluster sampling method was used to investigate 376 college students with cultural values scale, self-monitoring scale, self-efficacy scale, and social network index scale, structural equation model was constructed using M-plus and SPSS.ResultsThe result indicated that individual horizontal collectivist cultural values positively predict social network index (β = 0.477). Self-monitoring plays an intermediary role between cultural values and social network index, and self-efficacy plays a moderating role between self-monitoring and social network index.ConclusionThe level of an individual’s social network activity is affected by the cultural values of horizontal collectivism and self-monitoring. Improving individual self-monitoring ability and self-efficacy can effectively improve the interpersonal relationships of college students.

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.

Defect detection is critical to industrial quality control in leather production engineering. The various sizes and locations of defects in leather, as well as significant differences within the same class and indistinctive variations between different classes of defects, contribute to the complexity of the problem. To address this challenge, we propose a Multi-Layer Residual Convolutional Attention (MLRCA) approach. MLRCA enhances its ability to capture both intra-class and inter-class differences by enhancing the semantic feature representation in the backbone network. To improve multiscale fusion effects, we also incorporate the MLRCA module into the feature pyramid network (FPN) and propose a new multi-layer residual convolution attention feature pyramid network (ML-FPN). This approach enables more accurate identification of leather defects at a more detailed level by selectively capturing contextual information from different domains. We then implement the Side-Aware Boundary Localization (SABL) detection head, which accurately locates defects and helps the network distinguish between similar defect categories for more precise positioning. To validate the effectiveness of our approach, we conducted ablation experiments on the created leather dataset. Comparative experiments demonstrate the excellent capability of our model to detect minor defects. The model achieved 83.4, 89.7, and 85.6 for the AP, AP50, and AP75 evaluation metrics. In addition, the model achieves 71.3, 89.9, and 88.9 for APS, APM, and APL. Our approach has been confirmed feasible through experimentation and provides new insights for automated leather defect detection methods.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.