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To overcome challenges in the traditional melt casting process of zine alloys, such as oxidative burnout, compositional segregation, and grain coarsening, this study carried out hot compression deformation tests on Zn-0.5Mg-0.05Fe alloys prepared by powder metallurgy. The results show that increasing deformation temperature and decreasing strain rate reduce rheological stress. The hot compression deformation process exhibits three phases, as rheological stress increases, work hardening, dynamic softening, and steady-state fluidization are observed, respectively. An intrinsic equation for the hot compression process is derived as = 1.334 × 1010 × [sinh(0.0053σ)]7.62947exp(-109.931691/RT). Processing conditions for Zn-0.5Mg-0.05Fe alloy are determined from a processing map, suggesting that a safe zone of 25°C–130 °C deformation temperatures with 0.13s−1-0.36s−1 strain rates, and 120°C–200 °C deformation temperatures with 0.01s−1-0.6s−1 strain rates. Electron Back-scattering Patterns (EBSD) and Transmission Electron Microscope (TEM) results show both discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) during the hot deformation compression process. DRX reduces deformation resistance, refines the grains, and improves the mechanical properties of the alloys. This study provides theoretical insights and process guidance for preparing degradable zinc alloys with excellent mechanical properties.

Abstract Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific importance. However, D. involucrata is now an endangered species and its natural range includes low pH soils which are increasingly impacted by acid rain, nitrogen deposition and imbalanced nutrient cycling. The combination of these stresses also poses the additional risk of aluminum (Al) toxicity. Since the responses of D. involucrata to low pH and aluminum toxicity have not been investigated previously, a hydroponic experiment was conducted to examine the growth of one year old D. involucrata saplings after 50 d growth in a range of pH and Al conditions. Plant biomass, morphology, antioxidant enzyme activity, mineral concentrations and plant ecological strategy were compared at pH 5.8 and pH 4.0 without added Al (AlCl3) and in 0.1, 0.2 and 0.5 mM Al at pH 4.0. Our results showed that compared with pH 5.8, pH 4.0 (without added Al) not only inhibited root and shoot growth but also limited accumulation of nitrogen (N) and phosphorus (P) in leaves of D. involucrate. However, low Al concentrations (0.1 and 0.2 mM Al) at pH 4.0 partially restored the aboveground growth and leaf N concentrations, suggesting an alleviation of H+ toxicity by low Al concentrations. Compared with low Al concentrations, 0.5 mM Al treatment decreased plant growth and concentrations of N, P, and magnesium (Mg) in the leaves, which demonstrated the toxicity of high Al concentration. The results based on plant ecological strategy showed that D. involucrate decreased the competitiveness and favored its stress tolerance as pH changed from 5.8 to 4.0. Meanwhile, the competitiveness and stress tolerance of D. involucrata increased and decreased at low Al concentrations, respectively, and decreased and increased at high Al concentration, respectively. These trade-offs in ecological strategy were consistent with the responses of growth and antioxidant enzyme activity, reflecting a sensitive adaptation of D. involucrata to acid and Al stresses, which may aid in sustaining population dynamics. These findings are meaningful for understanding the population dynamics of D. involucrata in response to aluminum toxicity in acid soils.

Abstract Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Abstract Timely understanding of the preservation status of archaeological human bones is the foundation for conducting scientific archaeological work. This paper applies Micro-CT technology to analyze the microscopic preservation status of ancient human femora unearthed from the Rui State site in Liangdai Village, Hancheng, Shaanxi, the Chejiasi Cemetery in Baoji, and the Ouerping Cemetery in Xizhou Village, Yushe, Shanxi, and obtained imaging results and cortical bone porosity (Ct.Po), bone volume fraction (BV/TV), and bone density (BMD) parameters for 9 samples. The results show that the poorly preserved fragile group has lower Ct.Po, BV/TV, and BMD, and macroscopically presents fragile and porous features; while the well-preserved dense group has relatively higher Ct.Po, BV/TV, and BMD, and macroscopically appears solid and dense. This study employs Micro-CT technology to analyze the micro-preservation status of human bones from historical periods, confirming the effectiveness of this technology in revealing the microstructure of ancient human bones, and providing a reference for establishing a human bone preservation status evaluation system.

Abstract Background Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. Methods In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. Results In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. Conclusion In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI.

Abstract Previous studies have found that loneliness affects cognitive functions in older persons. However, the influence of loneliness on different cognitive fields and the internal mechanism of the relationship are unclear. A total of 4772 older persons aged above 50 years (Mean = 65.31, SD = 6.96, 57.7% female) were included in this study. All the participants completed the characteristics scale, as well as the loneliness scale, leisure activity scale, and cognitive function tests in six domains. The results showed that 17.6% of participants had high loneliness, while 16.7% of participants had low loneliness. Associations were observed between higher levels of loneliness and lower scores in general cognitive ability, memory, and executive functions. Mediation analysis suggested that leisure activities, encompassing mental, physical, and social activities, were associated with cognitive functions in the context of loneliness. These results indicate that leisure activities may play a significant role in the relationship between loneliness and cognitive functions in older adults. The study highlights the importance of considering leisure activities in this demographic to potentially mitigate the adverse cognitive effects associated with loneliness.

The polymer composites with significantly higher permittivity and low loss tangent are vital for the advancement of advanced energy storage capacitors. However, the pursuit of elevated permittivity often comes at the cost of increased loss, imposing limitations on practical applications. In this work, we propose a novel approach of multi-layer composites, comprising positive and negative-ε′ layers. We systematically examine the influence of the relative positioning of single layers within 2-, 3-, and 5-layers structure, as well as the thickness ratio between the positive and negative permittivity layers, to unlock the potential for simultaneously achieving high permittivity, low loss, and moderate energy density. In a remarkable observation, the spatial stacking arrangement of a 5-layer composite (97679) exhibits a substantial increase in permittivity, achieving an impressive 847 as the thickness ratio reached to 1:1:20:1:1. This enhancement represents a remarkable 176-fold increase in permittivity and a one-order-of-magnitude reduction in dielectric loss compared to pristine PI matrix (ε' ≈ 4.8, tanδ ≈ 0.012 at 10 kHz). The 5-layer composite with the content of 97679 demonstrates an enhanced energy density (Ud) of up to 2.49 J/cm³ while concurrently exhibiting an exceptional efficiency (η) of 93.8%. The underlying mechanism responsible for these excellent properties presents that the BDS is influenced by the positioning of the positive-ε′ layer, and the dielectric constant is primarily governed by the arrangement of negative-ε′ layer. The strategic modulation of a multi-layer structure with positive and negative permittivity layers opens a novel design for enhancing energy storage density and tailoring dielectric performances.

Abstract Metallurgical slag such as solid waste generated in the steel industry carries environmental pollution risks, but it is rich in nutrients required by microalgae. Metallurgical slag used for carbon capture and biomass energy conversion has multiple benefits: (i) reduction and harmless treatment of metallurgical solid waste, (ii) assisting in carbon neutrality by efficient carbon fixation, and (iii) production of biodiesel from CO2. In this study, AOD, BOF, BFS, HVS, and VTS slag were applied to culture Chlorella pyrenoidosa (C. pyrenoidosa) with the regulation of growth, carbon fixation, and lipid synthesis. An excellent fixed amount of CO2 with 94.59 mg is obtained from C. pyrenoidosa biomass at BOF slag added (mass ratio of CO2 captured/microalgae/slag with 1.99/1.00/10.53) since high Ca/Mg mass ratio of 419 (8.38 mg/L Ca and 0.02 mg/L Mg), no Cr and low concentration of Al (0.04 mg/L) contribute to regulating antioxidant enzyme activity (SOD and POD) to resist ROS and improving PEPC activity to reduce carbon flux toward lipid to promote biomass synthesis. Both metal concentrations from Ca (5.86 mg/L), Mg (0.05 mg/L), Al (0.42 mg/L), and Cr (0.006 mg/L) and suitable pH (10.53) in AOD leaching solution at solid/liquid ratio of 0.5 g/L change carbon flow toward efficient lipid synthesis (47.07 wt%) by continuously providing raw materials and energy by regulating ACC, ME, and PEPC activities. High value‐added biodiesel with high concentrations of C16 and C18 methyl esters from lipid of C. pyrenoidosa is achieved, following other ecological and economic benefits including 197 mg CO2 captured and 2198 mg AOD applied with harmless. In this study, C. pyrenoidosa is cultured with elements from metallurgical slag solid waste, which promotes C. pyrenoidosa efficient carbon fixation to assist in carbon neutrality, and provides guidance for CO2 conversion to high‐value‐added products with low cost.

Abstract Introduction Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients’ long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy. Case presentation The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components. Conclusions Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.

Abstract Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

Abstract Background The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as “fit” by comprehensive geriatric assessment (CGA). Methods A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of “fit” (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). Results One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). Conclusion This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. Trial registration The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Abstract Elucidating the neural basis of fear allows for more effective treatments for maladaptive fear often observed in psychiatric disorders. Although the basal forebrain (BF) has an essential role in fear learning, its function in fear expression and the underlying neuronal and circuit substrates are much less understood. Here we report that BF glutamatergic neurons are robustly activated by social stimulus following social fear conditioning in male mice. And cell-type-specific inhibition of those excitatory neurons largely reduces social fear expression. At the circuit level, BF glutamatergic neurons make functional contacts with the lateral habenula (LHb) neurons and these connections are potentiated in conditioned mice. Moreover, optogenetic inhibition of BF-LHb glutamatergic pathway significantly reduces social fear responses. These data unravel an important function of the BF in fear expression via its glutamatergic projection onto the LHb, and suggest that selective targeting BF-LHb excitatory circuitry could alleviate maladaptive fear in relevant disorders.

Abstract Background Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling. Increasing evidence indicates that endothelial-to-mesenchymal transition (EndMT) in pulmonary artery endothelial cells (PAECs) is a pivotal trigger initiating this remodeling. However, the regulatory mechanisms underlying EndMT in PH are still not fully understood. Methods Cytokine-induced hPAECs were assessed using RNA methylation quantification, qRT-PCR, and western blotting to determine the involvement of N6-methyladenosine (m6A) methylation in EndMT. Lentivirus-mediated silencing, overexpression, tube formation, and wound healing assays were utilized to investigate the function of METTL3 in EndMT. Endothelial-specific gene knockout, hemodynamic measurement, and immunostaining were performed to explore the roles of METTL3 in pulmonary vascular remodeling and PH. RNA-seq, RNA Immunoprecipitation-based qPCR, mRNA stability assay, m6A mutation, and dual-luciferase assays were employed to elucidate the mechanisms of RNA methylation in EndMT. Results The global levels of m6A and METTL3 expression were found to decrease in TNF-α- and TGF-β1-induced EndMT in human PAECs (hPAECs). METTL3 inhibition led to reduced endothelial markers (CD31 and VE-cadherin) and increased mesenchymal markers (SM22 and N-cadherin) as well as EndMT-related transcription factors (Snail, Zeb1, Zeb2, and Slug). The endothelial-specific knockout of Mettl3 promoted EndMT and exacerbated pulmonary vascular remodeling and hypoxia-induced PH (HPH) in mice. Mechanistically, METTL3-mediated m6A modification of kruppel-like factor 2 (KLF2) plays a crucial role in the EndMT process. KLF2 overexpression increased CD31 and VE-cadherin levels while decreasing SM22, N-cadherin, and EndMT-related transcription factors, thereby mitigating EndMT in PH. Mutations in the m6A site of KLF2 mRNA compromise KLF2 expression, subsequently diminishing its protective effect against EndMT. Furthermore, KLF2 modulates SM22 expression through direct binding to its promoter. Conclusions Our findings unveil a novel METTL3/KLF2 pathway critical for protecting hPAECs against EndMT, highlighting a promising avenue for therapeutic investigation in PH.

Abstract Silicon Carbide (SiC) Gate Turn‐off (GTO) thyristor is regarded as a promising option for pulsed power applications; however, the formation of high di/dt has been constrained by the slow current rise transient phase and the turn‐on current heterogeneity over the chip device. In this paper, a practical integrated multi‐cell simulation is performed to physically characterize the turn‐on transient of SiC GTO thyristor. Through examining electrical coupling between adjacent cells caused by both parasitics of electrode metallization and carrier travelling via SiC, the current distributions are observed, and the carrier transport dynamics are analyzed in detail. Furthermore, physical mechanisms dominating the current heterogeneity among multi‐cells are discovered in depth. It is revealed that the current heterogeneity during the turn‐on transient is primarily resulted from the Gate signal delay caused by the Gate Runner metallization, and the lateral interaction from adjacent semiconductor regions adds to this inhomogeneity; however, this situation can be improved once the electrical distance between each Anode contact and the Anode electrode gets lowered. Design method for turn‐on performance improvement is also proposed accordingly. Besides, based on the analysis conducted on the multi‐cell simulation results, the possible reason of the extremely slow current rise transient phase is speculated and experimentally verified. The improvement in the comprehension of SiC GTO's turn‐on transient, which cannot be obtained from the traditional investigation from the viewpoint of one elementary cell, will provide guiding principles helping in directing future efforts to advance the improvement of device design technology.

Magnesium (Mg) is abundant in humans. Studies have shown that Mg2+ significantly affects physiological processes such as osteogenesis, osteoblast adhesion and motility, immunomodulation, and angiogenesis. Mg-based alloy porous scaffolds have attracted increasing attention because of their degradability and mechanical properties. Hence, wire-cut EDM was used to fabricate porous scaffolds. In addition, fluoride treatment afforded an MgF2 coating, and racemic polylactic acid PDLLA was used as the carrier of rhBMP-2, which was evenly coated on the surface of the passivated porous alloy scaffold to slowly release growth factors and slow down the degradation rate. The rat femoral condyle defect model experiment was performed to study the in vivo bone regeneration capacity of porous scaffolds and compare the differences in the healing effect with or without rhBMP-2. The enhanced corrosion resistance of the porous scaffold was confirmed through in vitro immersion experiments. Micro-CT implied that porous scaffold with rhBMP-2 induced new bone formation and the new bone formation along the pores, as well as the histological examination in vivo. In summary, the porous scaffold promotes bone formation and has great potential for clinical translation.

Composite structures with high strength and controllable fragments driven by implosions are valuable in weaponry. This study explored a technical approach to preparing heterogeneous-gradient composite plates with a sphere-array interlayer using explosive welding. TA1 and Q235B steel plates with various spherical grooves were employed as the flyer and base plates, respectively. The spherical grooves were filled with Q235 steel balls. Composite plates were formed by a single explosion using the parallel method, and the parameters adopted in the experiment were within a weldable window. The performance of the TA1/Q235 steel balls/Q235B composite plate was studied through microstructural observations and mechanical property testing. The results indicated that the two embedded spherical structure schemes (with steel balls protruding or not protruding from the plane of the base plate) created effective metallurgical bonding interfaces between the two plates and at the top of the spheres. Surface flatness plays a crucial role in forming wavy interfaces. The composite plates embedded with non-protruding spheres exhibited better mechanical properties, higher interface strength, and a more regular, wavy interface than those embedded with protruding spheres. The ultimate tensile strength of the composite plate containing a sphere with a diameter of 2 mm was similar to that of an intact composite plate. The fracture surfaces of the specimens embedded with spheres exhibited ductile and quasi-cleavage fracturing in the tensile and impact-toughness tests. The structure of the composite plates embedded with non-protruding spheres provides a strategy for preparing multifunctional warhead shells.

Abstract Background Surgical interventions are more effective than nonsurgical approaches in providing a cure for stress urinary incontinence (SUI). In this study, we aimed to assess the benefits of tension-free vaginal tape (TVT) abbrevo by comparing its efficacy and complications to those of TVT obturator. Methods and results 49 and 47 patients at The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University between January 2013 and December 2016 were included in the TVT-O and TVT-A groups, respectively. We evaluate the success rate and perioperative complications associated with TVT-O and TVT-A. A questionnaire that utilized the Patient Global Impression of Improvement (PGI-I) Scale was employed to assess the impact of surgery. Patients were followed up at 1 year, and 5 years after surgery. There were no statistically significant differences found in the efficacy of the TVT-A group and TVT-O group during both the one-year (p = 0.4) and five-year (p = 0.32) follow-up periods. In the period of one-year follow-up, 95.9% (n = 47) of patients in the TVT-O group and 95.8% (n = 45) of patients in the TVT-A group demonstrated improvement. During the period of five-year follow-up, 87.8% (n = 43) of patients in the TVT-O group and 93.6% (n = 44) of patients in the TVT-A group demonstrated improvement. Conclusions Based on our findings, TVT-A and TVT-O procedures exhibited similarly high success rates and low frequencies of complications.

Abstract In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress–strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.

Abstract This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Abstract Background Mucoepidermoid Carcinoma of the Esophagus (MECE) is a relatively rare tumor type, with most of the current data derived from case reports or small sample studies. This retrospective study reports on the 10-year survival data and detailed clinicopathological characteristics of 48 patients with esophageal MEC. Methods Data were collected from 48 patients who underwent curative surgery for esophageal MEC at the Fourth Hospital of Hebei Medical University between January 1, 2004, and December 31, 2020. These were compared with contemporaneous cases of Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC). Using the Kaplan-Meier method and multivariate Cox regression analysis, we investigated the clinicopathological factors affecting the survival of patients with MEC. Results The incidence of MECE was predominantly higher in males, with a male-to-female ratio of approximately 7:1. The mid-thoracic segment emerged as the most common site of occurrence. A mere 6.3% of cases were correctly diagnosed preoperatively. The lymph node metastasis rate stood at 35.4%. The overall 1-year, 3-year, 5-year, and 10-year survival rates for all patients were 85.4%, 52.1%, 37.0%, and 31.0%, respectively. Post 1:1 propensity score matching, no significant statistical difference was observed in the Overall Survival (OS) between MEC patients and those with Esophageal Squamous Cell Carcinoma (ESCC) and Esophageal Adenocarcinoma (EAC) (P = 0.119, P = 0.669). Univariate analysis indicated that T staging and N staging were the primary factors influencing the prognosis of esophageal MEC. Conclusions MECE occurs more frequently in males than females, with the mid-thoracic segment being the most common site of occurrence. The rate of accurate preoperative endoscopic diagnosis is low. The characteristic of having a short lesion length yet exhibiting significant extramural invasion may be a crucial clinicopathological feature of MECE. The OS of patients with MEC does not appear to significantly differ from those with esophageal squamous carcinoma and adenocarcinoma.

Abstract Background Cerebral malaria (CM) is the most lethal complication of malaria, and survivors usually endure neurological sequelae. Notably, the cytotoxic effect of infiltrating Plasmodium-activated CD8+ T cells on cerebral microvasculature endothelial cells is a prominent feature of the experimental CM (ECM) model with blood–brain barrier disruption. However, the damage effect of CD8+ T cells infiltrating the brain parenchyma on neurons remains unclear. Based on the immunosuppressive effect of the PD-1/PD-L1 pathway on T cells, our previous study demonstrated that the systemic upregulation of PD-L1 to inhibit CD8+ T cell function could effectively alleviate the symptoms of ECM mice. However, it has not been reported whether neurons can suppress the pathogenic effect of CD8+ T cells through the PD-1/PD-L1 negative immunomodulatory pathway. As the important inflammatory factor of CM, interferons can induce the expression of PD-L1 via different molecular mechanisms according to the neuro-immune microenvironment. Therefore, this study aimed to investigate the direct interaction between CD8+ T cells and neurons, as well as the mechanism of neurons to alleviate the pathogenic effect of CD8+ T cells through up-regulating PD-L1 induced by IFNs. Methods Using the ECM model of C57BL/6J mice infected with Plasmodium berghei ANKA (PbA), morphological observations were conducted in vivo by electron microscope and IF staining. The interaction between the ECM CD8+ T cells (immune magnetic bead sorting from spleen of ECM mice) and primary cultured cortical neurons in vitro was observed by IF staining and time-lapse photography. RNA-seq was performed to analyze the signaling pathway of PD-L1 upregulation in neurons induced by IFNβ or IFNγ, and verified through q-PCR, WB, IF staining, and flow cytometry both in vitro and in vivo using IFNAR or IFNGR gene knockout mice. The protective effect of adenovirus-mediated PD-L1 IgGFc fusion protein expression was verified in ECM mice with brain stereotaxic injection in vivo and in primary cultured neurons via viral infection in vitro. Results In vivo, ECM mice showed infiltration of activated CD8+ T cells and neuronal injury in the brain parenchyma. In vitro, ECM CD8+ T cells were in direct contact with neurons and induced axonal damage, as an active behavior. The PD-L1 protein level was elevated in neurons of ECM mice and in primary cultured neurons induced by IFNβ, IFNγ, or ECM CD8+ T cells in vitro. Furthermore, the IFNβ or IFNγ induced neuronal expression of PD-L1 was mediated by increasing STAT1/IRF1 pathway via IFN receptors. The increase of PD-L1 expression in neurons during PbA infection was weakened after deleting the IFNAR or IFNGR. Increased PD-L1 expression by adenovirus partially protected neurons from CD8+ T cell-mediated damage both in vitro and in vivo. Conclusion Our study demonstrates that both type I and type II IFNs can induce neurons to upregulate PD-L1 via the STAT1/IRF1 pathway mediated by IFN receptors to protect against activated CD8+ T cell-mediated damage, providing a targeted pathway to alleviate neuroinflammation during ECM. Graphical Abstract

Abstract Background To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . Methods The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. Results A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . Conclusion The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Abstract Background Episodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer’s disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative. Result The present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males. Conclusions Our study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.

The milk fat globule membrane (MFGM) is a complex structure with numerous functions, and its composition is affected by many factors. There have been few systematic investigations on goat MFGM proteome profiling during lactation. Individual milk samples from 15 healthy dairy goats were obtained at six lactation time points for investigation of the MFGM proteome using both data-independent acquisition (DIA) and data-dependent acquisition (DDA) proteomics techniques combined with multivariate statistical analysis. Using the DIA method, 890 variably abundant MFGM proteins were discovered throughout the lactation cycle. From 1 to 240 d, butyrophilin subfamily 1 member A1, lipoprotein lipase, perilipin-2, and adipose triglyceride lipase were upregulated, while APOE, complement C3, clusterin, and IgG were downregulated. Furthermore, from 1 to 90 d, annexin A1, annexin A2, and antithrombin-III were downregulated, then upregulated by d 240. Albumin had a high degree of connectedness, indicating that it was a key protein, according to protein–protein interaction research. Overall, our findings gave new insights into the biological features of MFGM protein in goat milk throughout lactation, which may aid in the creation of specialized MFGM products and infant formula.

Summary: Background: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. Methods: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y–V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. Results: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y–V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. Conclusion: Constricted posterior fourchette seriously affects the quality of life. Y–V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.

ABSTRACT: The distribution of mineral elements in milk is crucial for their absorption and utilization, however, there has been limited attention given to the status of mineral elements in goat milk. In this study, goat milk was collected at 4 lactation periods (1–3, 90, 150, 240 d) and separated into 4 fractions (fat, casein, whey, and aqueous phase). The concentrations of Mg, Ca, Na, K, Zn, Fe, Cu, Mn, Co, Ni, Mo, and Cr in 4 fractions were analyzed using an inductively coupled plasma emission spectrometer. Our findings reveal that Ca, Zn, Fe, Cu, Mn, and Cr exhibit the highest levels in casein, while Mo demonstrates the highest content in whey. Additionally, Mg, Na, K, and Ni display the highest concentrations in the aqueous phase. Specifically, the contents of Ca, Cu and Fe in casein decrease from 1–3 to 150 d of lactation but increase from 150 to 240 d of lactation. Furthermore, the content of Mg in the aqueous phase decreases from 1–3 to 90 d of lactation but increases from 90 to 240 d of lactation. The content of Na and K in the aqueous phase decreases from 1–3 to 150 d of lactation. Notably, the content of Mo in whey increases from 1–3 to 150 d of lactation and decreases from 150 to 240 d. Our research contributes to the advancement of understanding the bioavailability of mineral elements in goat milk.

This paper proposes an improvement in the test method for determining the flexural dynamic modulus of elasticity of strawboard with two triangular prisms as supports, for quality control and classification. Free-plate modal and free-plate transient excitation methods were used to test the elastic modulus of 1/4-plate and whole-plate strawboards. The dynamic test results were verified with the four-point bending method and tensile method. The results show that the elastic moduli of strawboards is approximately 2 GPa. The dynamic test method proposed is efficient, simple, repeatable, and accurate. This method is more suitable for factory applications than existing dynamic testing methods. The framed cases produced by the strawboard all meet the performance requirements in GB/T 7284 (2016).

The distribution pattern of metals as active centers on a substrate can influence the peroxymonosulfate (PMS) activation and contaminants degradation. Herein, atomic layer deposition is applied to prepare Cu single atom (SA-Cu), cluster (C-Cu), and film (F-Cu) decorated MXene catalysts by regulating the number of deposition cycles. In comparison with SA-Cu-MXene (adsorption energy (Eads) = −4.236 eV) and F-Cu-MXene (Eads = −3.548 eV), PMS is shown to adsorb preferably on the C-Cu-MXene surface for activation (Eads = −5.435 eV), realizing higher utilization efficiency. More SO4·− are generated in C-Cu-MXene/PMS system with steady-state concentration and 1–3 orders of magnitude higher than those in the SA-Cu-MXene and F-Cu-MXene activated PMS systems. Particularly, the contribution of SO4·− oxidation to sulfamethoxazole (SMX) degradation followed the order, C-Cu-MXene (97.3%) > SA-Cu-MXene (90.4%) > F-Cu-MXene (71.9%), realizing the larger SMX degradation rate in the C-Cu-MXene/PMS system with the degradation rate constants (k) at 0.0485 min−1. Additionally, SMX degradation routes in C-Cu-MXene/PMS system are found with fewer toxic intermediates. Through this work, we highlighted the importance of guided design of heterogeneous catalysts in the PMS system. Appropriate metal distribution patterns need to be selected according to the actual water treatment demand. Metal sites could be then fully utilized to produce specific active species to improve the utilization efficiency of the oxidants.

目的 本研究对烟雾病患者血管样本的差异表达基因（differentially expressed genes，DEGs）进行生物信息学鉴定和分析，旨在探讨烟雾病的潜在发病机制。 方法 本研究以烟雾病和颈内动脉瘤患者大脑血管样本为研究对象。利用R语言线性模型微阵列数据（linear models for microarray data，limma）分析包对基因表达综合数据库（gene expression omnibus，GEO）中的GSE141025数据集进行分析，该数据集涵盖4例烟雾病患者和4例颈内动脉瘤患者的大脑中动脉和颞浅动脉样本各1个，共计16个样本。选择烟雾病患者的大脑中动脉、颞浅动脉及颈内动脉瘤患者的颞浅动脉共12个样本进行DEGs筛选。通过R语言功能富集分析工具包clusterProfiler，对筛选出的DEGs进行基因本体（gene ontology，GO）富集分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路分析。利用STRING数据库构建蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络，并使用网络可视化软件Cytoscape进行蛋白质网络的可视化和枢纽基因筛选。 结果 本研究在烟雾病患者的大脑中动脉与颞浅动脉样本间鉴定出138个DEGs，包括18个上调基因和120个下调基因。GO富集分析显示，以上DEGs在细胞外基质、受体配体活性和生长因子活性等方面显著富集，可能与烟雾病相关的血管病变和神经保护机制有关。KEGG通路分析提示，DEGs主要在酪氨酸代谢通路中富集。通过PPI网络分析，共筛选出9个枢纽基因，包括骨膜蛋白（periostin，POSTN）、脑源性神经营养因子（brain derived neurotrophic factor，BDNF）、血小板衍生生长因子受体α（platelet derived growth factor receptor alpha，PDGFRA）、Thy-1细胞表面抗原（Thy-1 cell surface antigen，THY1）、ⅩⅤ型胶原蛋白α1链（collagen type ⅩⅤ alpha 1 chain，COL15A1）、成纤维细胞生长因子7（fibroblast growth factor 7，FGF7）、光蛋白聚糖（lumican，LUM）、层粘连蛋白α2亚基（laminin subunit alpha 2，LAMA2）和RELN（reelin）。此外，上调基因delta样典型Notch配体4（delta like canonical Notch ligand 4，DLL4）在本研究中首次被发现可能在烟雾病中扮演重要角色，或与烟雾病的病理性血管生成有关。 结论 细胞外基质、生长因子及其受体的表达失调等可能参与烟雾病的发病过程。DEGs分析筛选出的枢纽基因（POSTN、BDNF、PDGFRA、THY1、COL15A1、FGF7、LUM、LAMA2、RELN）以及DLL4可能在烟雾病的病理形成过程中发挥作用。 Abstract: Objective In this study, bioinformatics analysis of differentially expressed genes (DEGs) between blood vessel samples of patients with moyamoya disease were conducted to explore the potential pathogenesis of moyamoya disease. Methods The cerebral blood vessel samples from patients with moyamoya disease and internal carotid aneurysm were taken as research subjects. The linear models for microarray data (limma) package in R was used to analyze the GSE141025 dataset downloaded from the gene expression omnibus (GEO). The dataset included samples from 4 moyamoya disease patients and 4 internal carotid aneurysm patients, providing a total of 16 samples including one middle cerebral artery and one superficial temporal artery from each patient. A total of 12 samples of middle cerebral artery and superficial temporal artery from moyamoya disease patients and superficial temporal artery from internal carotid aneurysm patients were selected for DEGs screening. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis on the DEGs were conducted using the clusterProfiler package in R. The STRING database was utilized to construct the protein-protein interaction (PPI) network, and the network visualization software Cytoscape was used to visualize the protein network and to filter hub genes. Results In the comparison between middle cerebral artery and superficial temporal artery samples from patients with moyamoya disease, 138 DEGs were identified, including 18 up-regulated genes and 120 down-regulated genes. GO enrichment analysis revealed that these DEGs were significantly enriched in extracellular matrix, receptor ligand activity, and growth factor activity, suggesting their potential involvement in vasculopathy and neuroprotective mechanisms associated with moyamoya disease. KEGG pathway analysis indicated that DEGs were primarily enriched in the tyrosine metabolic pathway. Through PPI network analysis, 9 hub genes were filtered, including periostin (POSTN), brain derived neurotrophic factor (BDNF), platelet derived growth factor receptor alpha (PDGFRA), Thy-1 cell surface antigen (THY1), collagen type ⅩⅤ alpha 1 chain (COL15A1), fibroblast growth factor 7 (FGF7), lumican (LUM), laminin subunit alpha 2 (LAMA2) and reelin (RELN). Additionally, the up-regulated gene delta like canonical Notch ligand 4 (DLL4) was firstly founded possibly associated with pathological angiogenesis of moyamoya disease in this study, suggesting that it may play a significant role in moyamoya disease. Conclusions The study indicates that the dysregulation of the expression of extracellular matrix components, growth factors and their receptors might be involved in the pathogenesis of moyamoya disease. The hub genes selected by DEGs analysis (POSTN, BDNF, PDGFRA, THY1, COL15A1, FGF7, LUM, LAMA2, RELN) and DLL4 may play a role in the pathological process of moyamoya disease.

Abstract Objective To compare the similarities and differences between patients with Coronavirus Disease 2019 (COVID-19) and those with other community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU), utilizing propensity score matching (PSM), regarding hospitalization expenses, treatment options, and prognostic outcomes, aiming to inform the diagnosis and treatment of COVID-19. Methods Patients admitted to the ICU of the Third People’s Hospital of Datong City, diagnosed with COVID-19 from December 2022 to February 2023, constituted the observation group, while those with other CAP admitted from January to November 2022 formed the control group. Basic information, clinical data at admission, and time from symptom onset to admission were matched using PSM. Results A total of 70 patients were included in the COVID-19 group and 119 in the CAP group. The patients were matched by the propensity matching method, and 37 patients were included in each of the last two groups. After matching, COVID-19 had a higher failure rate than CAP, but the difference was not statistically significant (73% vs. 51%, p = 0.055). The utilization rate of antiviral drugs (40% vs. 11%, p = 0.003), γ-globulin (19% vs. 0%, p = 0.011) and prone position ventilation (PPV) (27% vs. 0%, p

Abstract It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.

The focus of this paper was to explore the stability issues associated with delayed neural networks (DNNs). We introduced a novel approach that departs from the existing methods of using quadratic functions to determine the negative definite of the Lyapunov-Krasovskii functional's (LKFs) derivative $ \dot{V}(t) $. Instead, we proposed a new method that utilizes the conditions of positive definite quadratic function to establish the positive definiteness of LKFs. Based on this approach, we constructed a novel the relaxed LKF that contains delay information. In addition, some combinations of inequalities were extended and used to reduce the conservatism of the results obtained. The criteria for achieving delay-dependent asymptotic stability were subsequently presented in the framework of linear matrix inequalities (LMIs). Finally, a numerical example confirmed the effectiveness of the theoretical result.

Abstract Background Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. Methods The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58 hep−/− . The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). Results Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. Conclusions This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Abstract Background and objectives Aging poses a significant challenge worldwide, with China’s aging status becoming particularly severe. What is the impact of Internet use on the health of the elderly? Existing studies have drawn conflicting conclusions that Internet use improves or harms health. The purpose of this study was to explore how Internet use affects the health of older adults, and the mechanisms and heterogeneity of these effects. Research design and methods Based on Grossman’s theory, this paper constructs a health production function model. Using the data of China Family Panel Studies (CFPS) from 2014 to 2020, we investigated the impact of Internet use on the health of older adults using fixed effect model and instrumental variable method. We also examined the mediating role of health information acquisition, lifestyle, and social interaction in these associations. Results Internet use is positively associated with self-rated health and negatively associated with psychological sub-health level. Internet use promotes the health of older adults by facilitating access to health information, healthy lifestyles, and enhancing social interaction. And the impacts are heterogeneous at the individual and regional levels. Discussion and implications We should progressively enhance the level of internet accessibility for older adults, while concurrently addressing and narrowing the ‘digital divide’. By generating an abundance of superior health-related information, we can significantly improve health education tailored for the elderly. Additionally, it is crucial to offer extensive training opportunities designed to equip older adults with the necessary skills to proficiently navigate the internet.

Abstract Background Culex pipiens pallens and Culex pipiens quinquefasciatus are the dominant species of Culex mosquitoes in China and important disease vectors. Long-term use of insecticides can cause mutations in the voltage-gated sodium channel (vgsc) gene of mosquitoes, but little is known about the current status and evolutionary origins of vgsc gene in different geographic populations. Therefore, this study aimed to determine the current status of vgsc genes in Cx. p. pallens and Cx. p. quinquefasciatus in China and to investigate the evolutionary inheritance of neighboring downstream introns of the vgsc gene to determine the impact of insecticides on long-term evolution. Methods Sampling was conducted from July to September 2021 in representative habitats of 22 provincial-level administrative divisions in China. Genomic DNA was extracted from 1308 mosquitoes, the IIS6 fragment of the vgsc gene on the nerve cell membrane was amplified using polymerase chain reaction, and the sequence was used to evaluate allele frequency and knockdown resistance (kdr) frequency. MEGA 11 was used to construct neighbor-joining (NJ) tree. PopART was used to build a TCS network. Results There were 6 alleles and 6 genotypes at the L1014 locus, which included the wild-type alleles TTA/L and CTA/L and the mutant alleles TTT/F, TTC/F, TCT/S and TCA/S. The geographic populations with a kdr frequency less than 20.00% were mainly concentrated in the regions north of 38° N, and the geographic populations with a kdr frequency greater than 80.00% were concentrated in the regions south of 30° N. kdr frequency increased with decreasing latitude. And within the same latitude, the frequency of kdr in large cities is relatively high. Mutations were correlated with the number of introns. The mutant allele TCA/S has only one intron, the mutant allele TTT/F has three introns, and the wild-type allele TTA/L has 17 introns. Conclusions Cx. p. pallens and Cx. p. quinquefasciatus have developed resistance to insecticides in most regions of China. The neighboring downstream introns of the vgsc gene gradually decreased to one intron with the mutation of the vgsc gene. Mutations may originate from multiple mutation events rather than from a single origin, and populations lacking mutations may be genetically isolated. Graphical Abstract

Abstract Background Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016–2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate. Results Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified. Conclusion This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes.

Abstract Background Environmental stresses negatively impact reproductive development and yield. Drought stress, in particular, has been examined during Arabidopsis reproductive development at morphological and transcriptomic levels. However, drought-responsive transcriptomic changes at different points in reproductive development remain unclear. Additionally, an investigation of the entire transcriptome at various stages during flower development is of great interest. Results Here, we treat Arabidopsis plants with well-watered and moderately and severely limiting water amounts when the first flowers reach maturity and generate RNA-seq datasets for early, middle, and late phases during flower development at 5, 6, and 7 days following treatment. Under different drought conditions, flowers in different developmental phases display differential sets of drought-responsive genes (DTGs), including those that are enriched in different GO functional categories, such as transcriptional regulation and response to stresses (early phase), lipid storage (middle phase), and pollen and seed development and metabolic processes (late phase). Some gene families have different members induced at different floral phases, suggesting that similar biochemical functions are carried out by distinct members. Developmentally-regulated genes (DVGs) with differential expression among the three floral phases belong to GO terms that are similar between water conditions, such as development and reproduction, metabolism and transport, and signaling and stress response. However, for different water conditions, such similar GO terms correspond to either distinct gene families or different members of a gene family, suggesting that drought affects the expression of distinct families or family members during reproductive development. A further comparison among transcriptomes of tissues collected on different days after treatment identifies differential gene expression, suggesting age-related genes (ARGs) might reflect the changes in the overall plant physiology in addition to drought response and development. Conclusion Together, our study provides new insights into global transcriptome reprogramming and candidate genes for drought response, flower development, aging and coordination among these complex biological processes.

Abstract Objective To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province. Methods A single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18–75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT). Results The eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%–95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%–98.4%), 92.7% (38/41, 95%CI 84.4%–101.0%),88.4% (38/43，95%CI 78.4%–98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P

Abstract Background Clear cell renal cell carcinoma (ccRCC) is associated with a high prevalence of cancer-related deaths. The survival rates of patients are significantly lower in late-stage ccRCC than in early-stage ccRCC, due to the spread and metastasis of late-stage ccRCC, surgery has not reached the goal of radical cure, and the effect of traditional radiotherapy and chemotherapy is poor. Thus, it is crucial to accurately assess the prognosis and provide personalized treatment at an early stage in ccRCC. This study aims to develop an efficient nomogram model for stratifying and predicting the survival of ccRCC patients based on tumor stage. Methods We first analyzed the microarray expression data of ccRCC patients from the Gene Expression Omnibus (GEO) database and categorized them into two groups based on the disease stage (early and late stage). Subsequently, the GEO2R tool was applied to screen out the genes that were highly expressed in all GEO datasets. Finally, the clinicopathological data of the two patient groups were obtained from The Cancer Genome Atlas (TCGA) database, and the differences were compared between groups. Survival analysis was performed to evaluate the prognostic value of candidate genes (PSAT1, PRAME, and KDELR3) in ccRCC patients. Based on the screened gene PSAT1 and clinical parameters that were significantly associated with patient prognosis, we established a new nomogram model, which was further optimized to a single clinical variable-based model. The expression level of PSAT1 in ccRCC tissues was further verified by qRT-PCR, Western blotting, and immunohistochemical analysis. Results The datasets GSE73731, GSE89563, and GSE150404 identified a total of 22, 89, and 120 over-expressed differentially expressed genes (DEGs), respectively. Among these profiles, there were three genes that appeared in all three datasets based on different stage groups. The overall survival (OS) of late-stage patients was significantly shorter than that of early-stage patients. Among the three candidate genes (PSAT1, PRAME, and KDELR3), PSAT1 was shown to be associated with the OS of patients with late-stage ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, neoadjuvant therapy, and PSAT1 level were significantly associated with patient prognosis. The concordance indices were 0.758 and 0.725 for the 3-year and 5-year OS, respectively. The new model demonstrated superior discrimination and calibration compared with the single clinical variable model. The enhancer PSAT1 used in the new model was shown to be significantly overexpressed in tissues from patients with late-stage ccRCC, as demonstrated by the mRNA level, protein level, and pathological evaluation. Conclusion The new prognostic prediction nomogram model of PSAT1 and clinicopathological variables combined was thus established, which may provide a new direction for individualized treatment for different-stage ccRCC patients.

Abstract Background Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients. Methods CC patients’ relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm. Results Eight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746–0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine. Conclusions An eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.

Abstract Background Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. Main text This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health. Graphical Abstract

Abstract How does Tencent—a leading Chinese Internet enterprise—frame news to regulate popular nationalism? To address this problem, we applied the automated sentiment analysis program to more than 500,000 news comments on the Tencent news website during the 2012 Diaoyu (Senkaku) Islands incident. The results show that audiences’ online nationalism is significantly influenced by Tencent news, user engagement, and emotions. First, contrary to using stimulative nationalist narratives in the early stages of the incident, the platform shifts to restrictive nationalist narratives to prevent online nationalism from endangering social governance; second, restrictive news can decrease popular nationalism compared with stimulative news; third, users’ love, anger, and disgust emotion can increase their support for China, while the happiness emotion has the opposite effect. Online nationalism, as imaginary engagement, arises from the collusion among platforms, the government, and audiences, contributing to maintaining the government’s legitimacy. The computational approach promises to shed light on nationalism research.

Abstract Ferroptosis is a novel form of programmed death, dependent on iron ions and oxidative stress, with a predominant intracellular form of lipid peroxidation. In recent years, ferroptosis has gained more and more interest of people in the treatment mechanism of targeted tumors. mTOR, always overexpressed in the tumor, and controlling cell growth and metabolic activities, has an important role in both autophagy and ferroptosis. Interestingly, the selective types of autophay plays an important role in promoting ferroptosis, which is related to mTOR and some metabolic pathways (especially in iron and amino acids). In this paper, we list the main mechanisms linking ferroptosis with mTOR signaling pathway and further summarize the current compounds targeting ferroptosis in these ways. There are growing experimental evidences that targeting mTOR and ferroptosis may have effective impact in many tumors, and understanding the mechanisms linking mTOR to ferroptosis could provide a potential therapeutic approach for tumor treatment.

The issue of whether CoCrFeNi is a single-phase or dual-phase high-entropy alloy (HEA) has long been in dispute. In this study, CoCrFeNi has been verified to be a dual-phase HEA composed of dendritic phases with an FCC structure and inter-dendritic phases with a BCC structure. The BCC phases within inter-dendritic regions are identified as Cr3O oxides which form inevitably under the arc-melting process. Undercooling treatment under a strong magnetic field can regulate the composition and precipitation of the BCC phase, refine the grain size, and enhance the solid solubility, consequently, the mechanical performances of CoCrFeNi HEA are effectively enhanced.

Grid-tie voltage source converters (VSCs) can operate in three distinct modes: AC-dominant, DC-dominant, and balanced, depending on the placement of the stiff voltage sources. The distinct operation modes of the VSCs traditionally demand different synchronization control techniques, leading to heterogeneous VSCs. It is challenging for the power system to accommodate and coordinate heterogeneous VSCs. A promising universal synchronization control technique for VSCs is the DC-link voltage synchronization control (DVSC) based on a lead compensator (LC). The LC DVSC stabilizes both the DC and AC voltages of a VSC while achieving synchronization with the AC grid. This results in a dual-port grid-forming (DGFM) characteristic for the VSC. However, there has been very limited study on the stability and synchronization controller design of the VSCs with the LC DVSC operating in various modes. To bridge this gap, the paper presents a quantitative analysis on the stability and steady-state performance of the LC DVSC in all three operation modes of the DGFM VSC. Based on the analysis, the paper provides step-by-step design guidelines for the LC DVSC. Furthermore, the paper uncovers an instability issue related to the LC DVSC when the DGFM VSC operates in the balanced mode. To tackle the instability issue, a virtual resistance control is proposed and integrated with the LC DVSC. Simulation results validate the analysis and demonstrate the effectiveness of the DGFM VSC with the LC DVSC designed using the proposed guidelines in all three operation modes. Overall, the paper demonstrates the feasibility of employing the DGFM VSC with the LC DVSC for all three possible operation modes, which can help overcome the challenges associated with accommodating and coordinating heterogeneous VSCs in the power system.

Medical image generation has recently garnered significant interest among researchers. However, the primary generative models, such as Generative Adversarial Networks (GANs), often encounter challenges during training, including mode collapse. To address these issues, we proposed the AE-COT-GAN model (Autoencoder-based Conditional Optimal Transport Generative Adversarial Network) for the generation of medical images belonging to specific categories. The training process of our model comprises three fundamental components. The training process of our model encompasses three fundamental components. First, we employ an autoencoder model to obtain a low-dimensional manifold representation of real images. Second, we apply extended semi-discrete optimal transport to map Gaussian noise distribution to the latent space distribution and obtain corresponding labels effectively. This procedure leads to the generation of new latent codes with known labels. Finally, we integrate a GAN to train the decoder further to generate medical images. To evaluate the performance of the AE-COT-GAN model, we conducted experiments on two medical image datasets, namely DermaMNIST and BloodMNIST. The model’s performance was compared with state-of-the-art generative models. Results show that the AE-COT-GAN model had excellent performance in generating medical images. Moreover, it effectively addressed the common issues associated with traditional GANs.

The integration of underground coal gasification (UCG) and carbon emission reduction is expected to become an excellent green energy technology during the transitional stage from the current to the arrival of carbon neutrality, and even play an important role in the longer history of carbon neutrality in the future. Looking back at the research history and current situation, the systematic strategy for UCG emission reduction has been basically formed, which can be summarized into five specific approaches. Among them, the targeted underground in-situ regulation can reduce the CO2 release and promote the quality and yield increase of UCG synthesis gas, and the relevant strategies and approaches can be summarized as the Carbon Regulation and Reduction (CRR). There are many research achievements on the supercritical gas storage of UCG-CO2 in underground space, mainly focusing on storage media, storage space, storage capacity, etc., with some discussions for storage mechanisms. The mineralization and storage of UCG-CO2 in underground space are not constrained by the harsh conditions of geological stability and sealing, and there is a potential dual effect of both carbon sequestration and gas conversion, but there are not many research results yet. The previous exploration of UCG-CO2 reinjection, utilization and storage focuses on two aspects, such as enhancing coalbed methane production and improving the production of UCG synthesis gas, and a series of explorations have been initiated for the emission reduction and utilization of CO2 from the tail gas of UCG hydrogen production in recent years. The CRR, as an active emission reduction strategy, targetedly reduces the CO2 concentration in the UCG synthesis gas by adjusting the gasifying agent and its injection method, and there are many theoretical achievements and preliminary on-site verification, which are expected to become a practical clean coal technology that integrates clean energy production and carbon reduction. Reviewing the progress and analyzing the shortcomings, the scientific and technological research for UCG carbon emission reduction has made many substantial achievements, but also still faces some challenges of sustainable development, and the future study should focus on four aspects. One is to prioritize the development of UCG-CO2 underground conversion and utilization technology with a focus on the UCG-CRR based on feasibility. The second is to focus on the shortcomings and to strive for the breakthrough of the collaborative mechanism and key technological bottlenecks of both UCG emission reduction and synthesis gas quality improvement. The third is to make solid progess and promote the prior implementation of UCG-CRR pilot tests and engineering demonstrations for the achievement of practical results step by step. The fourth is to ensure the implementation and establishment of the “trinity” policy support system for the UCG emission reduction consisting of carbon neutrality and management strategy, special science and technology action plans, and professional talent training.

This paper reports an experimental on the flexural performance of prestressed concrete-encased high-strength steel beams (PCEHSSBs). To study the applicability of high-strength steel (HSS) in prestressed concrete-encased steel beams (PCESBs), one simply supported prestressed concrete-encased ordinarystrength steel beam (PCEOSSB) and eight simply supported PCEHSSBs were tested under a four-point bending load. The influence of steel strength grade, I-steel ratio, reinforcement ratio and stirrup ratio on the flexural performance of such members was investigated. The test results show that increasing the I-steel grade and I-steel ratio can significantly improve the bearing capacity of PCESB. Increasing the compressive reinforcement ratio of PCEHSSB can effectively improve its bearing capacity and ductility properties, making full use of the performance of HSS in composite beams. Increasing the hoop ratio has a small improvement on the load capacity of the test beams; setting up shear connectors can improve the ductile properties of the specimens although it does not lead to a significant increase in the load capacity of the combined beams. Then, combined with the test data, the comprehensive reinforcement index considering the location of reinforcement was proposed to evaluate the crack resistance of specimens. The relationship between the comprehensive reinforcement index and the crack resistance of specimens was given.