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Non-small cell lung cancer (NSCLC) is a highly malignant tumor with a poor prognosis. Hypoxia conditions affect multiple cellular processes promoting the adaptation and progression of cancer cells via the activation of hypoxia-inducible factors (HIF) and subsequent transcription activation of their target genes. Preliminary studies have suggested that estrogen receptor β (ERβ) might play a promoting role in the progression of NSCLC. However, the precise mechanisms, particularly its connection to HIF-1α-mediated modulation under hypoxia, remain unclear. Our findings demonstrated that the overexpression of ERβ, not ERα, increased cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts. Tissue microarray staining revealed a strong correlation between the protein expression of HIF-1α and ERβ. HIF-1α induced ERβ gene transcription and protein expression in CoCl2-induced hypoxia, 1% O2 incubation, or HIF-1α overexpressing cells. ChIP identified HIF-1α binding to a hypoxia response element in the ESR2 promoter. The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the tumor growth, thus emphasizing the promising prospects of targeting HIF-1α and ERβ as a therapeutic approach for the treatment of NSCLC. Key messages: ERβ, not ERα, increases cell proliferation and inhibition of apoptosis in NSCLC cells and xenografts. A strong correlation exists between the protein expression of HIF-1α and ERβ. HIF-1α induced ERβ gene transcription and protein expression in hypoxic cells via binding to HRE in the ESR2 promoter. The suppression of HIF-1α and ERβ both in vitro and in vivo effectively reduced the NSCLC tumor growth. [ABSTRACT FROM AUTHOR]

In the clinical setting, cisplatin-induced nephrotoxicity primarily manifests as acute kidney injury (AKI). Recent studies have indicated that ferroptosis, a type of iron-dependent cell death, is closely involved in the cisplatin nephrotoxicity. AlkB homologue 5 (ALKBH5), an N6-methyladenosine (m6A) eraser protein expressed in various tissues, including the kidneys, has been implicated in this process. However, the specific role of ALKBH5 in cisplatin-induced nephrotoxicity remains unknown. Our findings indicated that ALKBH5 was upregulated in cisplatin-induced AKI, and the in vivo study results were consistent with the results of the in vitro study. Additionally, ALKBH5 knockout in transgenic animals was found to mitigate cisplatin-induced renal dysfunction, whereas its knock-in exacerbated the effects. Our study revealed that ALKBH5 controls the traditional ferroptosis metabolic pathway, leading to worsening of AKI in experiments conducted both in vivo and in vitro. The efficacy of pharmacological intervention targeting ALKBH5 in AKI animal models was demonstrated, and ALKBH5-based gene therapy confirmed these findings and displayed renoprotective effects against AKI. In conclusion, this study highlighted the crucial role of ALKBH5 as a key regulator of AKI. Overall, our research demonstrates the significant impact of ALKBH5 in controlling ferroptosis in cisplatin-induced AKI, suggesting that focusing on ALKBH5 could be a promising approach for treating cisplatin-related kidney damage. [ABSTRACT FROM AUTHOR]

Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based "2 × 2" symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10–9 M for human PD1 and 2.557 × 10–8 M for human CD47, respectively, where the CD47 binding is significantly weaker as compared to the binding affinity of HX008 to PD1 as well as the binding affinity of SIRPα-Fc to CD47, leading to little binding to RBCs and platelets and is contrasting to many CD47-agents in development. However, HX009 effectively and simultaneously binds to the PD1 and CD47 on PD1+CD47+ T-cells via cis-binding and elicits enhanced T cell activation compared to the parental HX008. HX009 caused little cytokine-release in human peripheral blood mononuclear cells. HX009 cross-species binds to cynomolgus monkey PD1/CD47 but not to rodents, making cynomolgus monkeys the choice of species to investigate the pharmacokinetics (PK) and toxicology of HX009. HX009's anti-tumor activities were confirmed in several humanized preclinical mouse models by determining either its anti-PD1 (humanized hu-CD47-MC38 models) or anti-CD47 (HuT-102 lymphoma CDX and three PDX-AML models) functions, although limited available humanized models have hindered broadly demonstration of enhanced anti-tumor activities contributed from the dual targeting of the BsAb. The expanded DLBCL-PDX trial data suggested that both EBV-status and OX40 expression could potentially be two positive predictors for response to HX009. An intravenous (IV) infusion PK study in cynomolgus monkey revealed its largely vasculature distribution, terminal half-life (T1/2) of ~ 50 h, and dose-proportional exposure without accumulation. The anti-drug antibody (ADA) was observed in all monkeys as expected, affecting the PK parameters of repeated administration. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009's candidacy for its clinical development. [ABSTRACT FROM AUTHOR]

In this paper, the authors consider the spectra of second-order left-definite difference operator with linear spectral parameters in two boundary conditions. First, they obtain the exact number of this kind of eigenvalue problem, and prove these eigenvalues are all real and simple. In details, they get that the number of the positive (negative) eigenvalues is related to not only the number of positive (negative) elements in the weight function, but also the parameters in the boundary conditions. Second, they obtain the interlacing properties of these eigenvalues and the sign-changing properties of the corresponding eigenfunctions according to the relations of the parameters in the boundary conditions. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications. Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway. [ABSTRACT FROM AUTHOR]

Optical fiber X-ray sensors have the potential to realize real-time dose monitoring of precision radiotherapy. However, an over-response phenomenon can occur when using an optical fiber sensor (OFXS) filled with inorganic scintillator (Gd2O2S:Tb) to measure the off-axis ratio (OAR) curve. The aim of this paper is to study the mechanism responsible for the over-response. Due to the complex particle distribution present in water phantoms, the Monte Carlo-based code GEANT4 was used to model the response of the scintillator. The energy response of the scintillator to photons and electrons was initially simulated, which subsequently allowed the OAR curve to be simulated and the results were compared with experiment. To analyze the energy distribution of particles in different positions, electron spectroscopy was simulated together with the photon spectrum at the position from the central axis to a distance of 14.5 cm away from the center. Finally, three metal (Al, Cu, Sn) caps were made for the OFXS to prevent the low-energy photons penetrating the OFXS, and the OARs measurements were repeated. The results show that the scintillator exhibits higher sensitivity to photons with energy below 0.5 MeV, while for electrons, the scintillator has a higher sensitivity to high-energy electrons. Simulations for electron spectroscopy and the photon spectrum show that there are many low-energy photons with relatively few low-energy electrons. The OARs measured using the OFXS with metal caps show that the over-response can be mitigated using a high-Z metal cap. The measurements demonstrate that the OAR cure measured using an OFXS fitted with a Sn cap exhibits the closest response to that measured using an IC. [ABSTRACT FROM AUTHOR]

. A sandwich-type photoelectrochemical (PEC) immunosensor based on a ZnO/poly(5-formylindole) (P5FIn)/anthocyanin heterostructure was developed to achieve sensitive background-free detection of the tumor marker CYFRA21-1. ZnO with good photovoltaic properties is combined with narrow bandgap P5FIn to form a p-n type heterojunction. This structure reduces the electron–hole pair recombination, thereby enhancing the photocurrent response of the composite. Anthocyanidins are environmentally friendly natural compounds with excellent antioxidant, redox properties, and remarkable electrochemical activity. After sensitization by anthocyanins, the absorption and utilization of visible light in the composites are enhanced, further improving the PEC luminescence efficiency of the materials. Additionally, boron nitride quantum dots (BN QDs) are combined with Ab2 via polydopamine (PDA) as a secondary antibody marker, enhancing its sensitivity. The biosensor exhibited a linear detection range of 0.001–100 ng mL−1 with a limit of detection (LOD) of 0.00033 ng mL−1. Furthermore, this biosensor demonstrates excellent selectivity, reproducibility, and stability, as well as successful results in analyzing actual human serum samples. This approach provides a feasible method for tumor marker detection. [ABSTRACT FROM AUTHOR]

Background: Chlorophenoxy compounds represent a group of selective herbicides widely used around the world. Chlorophenoxy herbicides are toxic, chemically stable, and can migrate into groundwater through soil leaching, posing a significant threat to drinking water safety and human health. Chlorophenoxy herbicides in groundwater aquifers are subject to anaerobic processes; however, the pathway and microbiology involved in the attenuation of chlorophenoxy herbicides under anaerobic condition are largely unknown. Here, the anaerobic degradation process of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a typical chlorophenoxy herbicide, was investigated. Results: The initial 52.5 ± 2.3 μM 2,4,5-T was completely degraded by a sediment-derived microbial consortium, with 3,4-dichlorophenol, 2,5-dichlorophenol, 3-chlorophenol (3-CP) and phenol being identified as the intermediate products. Reductive dechlorination of 3-CP to phenol and the subsequent elimination of phenol were the key transformation steps in the overall degradation process of 2,4,5-T. Amplicon sequencing suggested that Dehalobacter, Sulfuricurvum, Bacteroides, Acetobacterium, and Clostridium sensu stricto 7 might contribute to the transformation of 2,4,5-T to phenol, and Smithella, Syntrophorhabdus, Methanofollis and Methanosaeta likely cooperated to accomplish the complete mineralization of phenol. Conclusions: This study reported the anaerobic degradation of 2,4,5-T via reductive dechlorination and the subsequent syntrophic metabolization of phenol, an intermediate product transformed from 2,4,5-T. Dehalobacter was identified as the organohalide-respiring population catalyzing the reductive dechlorination reaction. Syntrophorhabdus and methanogenic populations were likely involved in anaerobic phenol oxidation and facilitated the complete mineralization of 2,4,5-T. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease. Interleukin (IL)-36 signalling may play a central role in GPP pathogenesis. Spesolimab is a humanized anti-IL-36 monoclonal antibody inhibiting the IL-36 signalling pathway. Here, we investigated the pharmacokinetics and safety of spesolimab in healthy Chinese subjects. Methods: In this Phase 1, single-dose, parallel-group, open-label study, healthy Chinese subjects aged 18–45 years received a single spesolimab dose by intravenous infusion (IV; 450 mg, 900 mg, or 1200 mg) or subcutaneous (SC) administration (300 mg or 600 mg). Primary endpoints were spesolimab exposure (area under the plasma concentration-time curve and maximum plasma concentration); secondary endpoints were treatment-emergent adverse events (TEAEs) and drug-related adverse events (AEs). Results: Fifty subjects received IV (n = 30) or SC (n = 20) spesolimab (n = 10 per dose group); 60.0% were male, mean ± standard deviation age was 31.5 ± 6.6 and 31.0 ± 6.5 years in the IV and SC groups, respectively. Spesolimab exposure increased in a dose-proportional manner in both groups. TEAEs were reported in 83.3% and 80.0% of subjects in the IV and SC groups, the most common TEAE was upper respiratory tract infection (20.0% and 25.0%, respectively). One serious AE of hand fracture was reported in the 900 mg IV group that was not considered drug-related. Drug-related AEs were reported in 53.3% and 55.0% of subjects in the IV and SC groups. All laboratory-related AEs were mild and resolved. Conclusion: Spesolimab exposure increased in a dose-proportional manner after a single dose by IV and SC administration. Spesolimab was well tolerated in healthy Chinese subjects. Clinical Trial Registration: Clinicaltrials.gov registration: NCT04390568. [ABSTRACT FROM AUTHOR]

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of −17.8%, 95% CI: −29.4%, −6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children. [ABSTRACT FROM AUTHOR]

Background: Left–right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left–right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. Methods: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). Results: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. Conclusion: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research. [ABSTRACT FROM AUTHOR]

Acetaldehyde (AL), a primary carcinogen, not only pollutes the environment, but also endangers human health after drinking alcohol. Here a promising bacterial strain was successfully isolated from a white wine cellar pool in the province of Shandong, China, and identified as Bacillus velezensis-YW01 with 16 S rDNA sequence. Using AL as sole carbon source, initial AL of 1 g/L could be completely biodegraded by YW01 within 84 h and the cell-free extracts of YW01 has also been detected to biodegrade the AL, which indicate that YW01 is a high-potential strain for the biodegradation of AL. The optimal culture conditions and the biodegradation of AL of YW01 are at pH 7.0 and 38 °C, respectively. To further analyze the biodegradation mechanism of AL, the whole genome of YW01 was sequenced. Genes ORF1040, ORF1814 and ORF0127 were revealed in KEGG, which encode for acetaldehyde dehydrogenase. Furthermore, ORF0881 and ORF052 encode for ethanol dehydrogenase. This work provides valuable information for exploring metabolic pathway of converting ethanol to AL and subsequently converting AL to carboxylic acid compounds, which opened up potential pathways for the development of microbial catalyst against AL. [ABSTRACT FROM AUTHOR]

In the AlxCoCrFeNi high entropy alloys (HEAs), adding Al promotes a microstructure shift from fcc to bcc or their mixtures, which increases the overall strength of the alloys. To understand the strengthening mechanism, it is crucial to study the microstructure and mechanical properties of each constitution phase with varying compositions in addition to the amounts of strengthening phases. However, systematic research on the strengthening effect of Al content in individual fcc and bcc phases is lacking. In the present work, seven AlxCoCrFeNi HEAs with different Al contents were prepared by arc melting. According to XRD, SEM and TEM observations and thermodynamic calculations, the phase constitutions of the alloys change in a sequence of fcc → fcc + A2 (disordered bcc) + B2 (ordered bcc) → A2 + B2 as the Al content increases. The addition of Al to the fcc phase generates substantial lattice distortion, but the nanoindentation hardness of the fcc phase is stabilized at about 3.6 GPa, meaning no solid solution hardening effect present in the fcc phase. However, with increasing Al content, the hardness of the bcc-based alloys increases, which is mostly attributable to the increasing amount of the B2 phase. [ABSTRACT FROM AUTHOR]

Profile shift is a highly effective technique for optimizing the performance of spur gear transmission systems. However, tooth surface wear is inevitable during gear meshing due to inadequate lubrication and long-term operation. Both profile shift and tooth surface wear (TSW) can impact the meshing characteristics by altering the involute tooth profile. In this study, a tooth stiffness model of spur gears that incorporates profile shift, TSW, tooth deformation, tooth contact deformation, fillet-foundation deformation, and gear body structure coupling is established. This model efficiently and accurately determines the time-varying mesh stiffness (TVMS). Additionally, an improved wear depth prediction method for spur gears is developed, which takes into consideration the mutually prime teeth numbers and more accurately reflects actual gear meshing conditions. Results show that consideration of the mutual prime of teeth numbers will have a certain impact on the TSW process. Furthermore, the finite element method (FEM) is employed to accurately verify the values of TVMS and load sharing ratio (LSR) of profile-shifted gears and worn gears. This study quantitatively analyzes the effect of profile shift on the surface wear process, which suggests that gear profile shift can partially alleviate the negative effects of TSW. The contribution of this study provides valuable insights into the design and maintenance of spur gear systems. [ABSTRACT FROM AUTHOR]

Background: Health literacy is one of the important determinants of healthy aging, yet few studies have focused on the association between health literacy and falls. Aims: This study aims to explore the relationship between health literacy and falls, with a focus on sex differences among older people in China. Methods: This cross-sectional study enrolled 2,144 older people aged ≥ 60 years from Shandong Province, China in 2021. We used general health literacy screening scale to assess health literacy, and collected the incidence of falls in the past year. Logistic regression models were employed to analyze the relationship between health literacy and falls. We investigated the sex differences by subgroup analyses. Results: The prevalence of adequate health literacy and falls was 21.7% (95% CI: 20.0–23.5%) and 25.4% (95% CI: 23.6–27.3%), respectively. In a fully-adjusted model, adequate health literacy was associated with a lower prevalence of falls in older adults (OR = 0.71, 95%CI: 0.52–0.96). Subgroup analysis revealed sex differences in this relationship (Pfor interaction <0.05). Specifically, the female group showed no significant relationship between health literacy and falls (OR = 0.92, 95% CI: 0.59–1.44); however, the male group demonstrated a robust and significant relationship (OR = 0.58, 95% CI: 0.37–0.90). Conclusions: Older people with adequate health literacy have lower prevalence of falls, which appears to differ by sex. This relationship was significant among men but not among women. These findings emphasize the need for policymakers and healthcare providers to consider sex differences when designing and implementing programs aimed at improving health literacy and preventing falls in the older population. Improving health literacy among older women could be a strategic component in bridging sex inequality in falls. [ABSTRACT FROM AUTHOR]

Co-combustion is a technology that enables the simultaneous and efficient utilization of biomass and coal gangue (CG). Nevertheless, the factors that affect the combustibility of co-pyrolytic char, which represents the rate-determining step of the entire co-combustion process, remain unclear. This study investigates the impact of the physicochemical properties of co-pyrolytic char, including pore structure, carbon structure, and alkali metals, on the combustion characteristics. The TGA analysis indicates that the ignition and burnout temperatures of the co-pyrolytic char increase as the CG mixing ratio increases, resulting in a prolonged combustion. This is due to the fact that the carbon structure of the co-pyrolytic char becomes increasingly aromatic, accompanied by a reduction in aliphatic hydrocarbons and oxygen-containing groups as the CG mixing ratio increases. Furthermore, the high ash content of the CG is another significant factor contributing to the observed reduction in combustibility. The reaction between mullite, quartz in CG, and alkali metals in biomass results in the formation of aluminosilicate, which reduces the catalytic ability of alkali metals. Furthermore, the char combustion kinetics are analyzed by the KAS method, and the results indicate that the introduction of CG increases the activation energy of the entire char combustion process. The activation energy of the 80RS20CG is within the range of 102.22–164.99 kJ/mol, while the RS char is within the range of 89.87–144.67 kJ/mol. [ABSTRACT FROM AUTHOR]

Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17–2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population. [ABSTRACT FROM AUTHOR]

In semi-arid regions, the positive feedback effect of vegetation and soil moisture plays an indispensable role in the process of water absorption by vegetation roots, and vegetation can also absorb water through the nonlocal interaction of roots. So in this paper, we consider how the interactions of cross-diffusion and nonlocal delay affect the growth of vegetation. By mathematical analysis, the conditions under which Turing patterns occur are obtained for this vegetation-water model. At the same time, we obtain the amplitude equation near the Turing bifurcation boundary by using the multi-scale analysis method. Conditions for the emergence of Turing patterns such as stripes, spots, and mixtures of stripes and spots are identified through the stability analysis of amplitude equation. Some numerical simulations are given to illustrate the analytical results, especially the evolution processes of vegetation patterns depicted under different parameters. [ABSTRACT FROM AUTHOR]

As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improving tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques. The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to develop new additives or natural whitening products to reduce the occurrence of side effects. [ABSTRACT FROM AUTHOR]

Purpose: Although there is a growing emphasis on supportive care for cancer patients, those with colorectal cancer (CRC) who have ostomies require special attention in terms of their physical, psychological, spiritual, and social needs. However, there has been a lack of significant progress in meeting the supportive care needs of CRC survivors with ostomies. To bridge this gap, we conducted a prospective longitudinal study to track the trends in supportive care needs among CRC survivors with ostomies and identify any predictors over 6-month period. Methods: A prospective longitudinal study was conducted at the wound and stoma clinic of Dalian University Affiliated Xinhua Hospital, focusing on CRC survivors with ostomies. A total of 143 participants completed self-report questionnaires on the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34-C (Mandarin)) and stoma complications at the first, third, and sixth month after surgery. ANOVA with repeated measure was utilized to assess the course of supportive care needs, with Generalized Estimating Equation (GEE) applied to identify predictors of SCNS. Results: The supportive care needs and five dimensions scores were statistically significant at three time points (P < 0.05). The ratings of patients at the first, third, and sixth month after surgery revealed a decreasing trend in the scores for patient care and support, psychological needs, physical and daily living needs, and health system and information needs. However, the score for sexual needs showed an increased tendency. Higher levels supportive care needs were generally connected with a short duration after ostomy, high income level, resident medical insurance, spouse caregiver, other chronic disease, and stoma complications. Conclusions: Survivors’ supportive care needs showed a dynamic trend over 6 months after surgery. Through three rounds, the primary needs were health system and information needs. It is recommended to integrate interdisciplinary health professionals and establish a comprehensive support and care system to effectively meet the diverse needs at different stages. Priority should be given to individuals with ostomies during the first and third month after surgery, particularly those with higher income levels, employee medical insurance, spouse caregivers, other chronic diseases, and stoma complications. [ABSTRACT FROM AUTHOR]

This paper concerns a diffusive predation model with nonlinear growth, cross-diffusion and protection zone terms. The main purpose is to investigate the effects of nonlinear growth and cross-diffusion on the coexistent solution when protection zone is present. Firstly, a priori estimate and the existence of positive solutions are discussed, including local and global existence. Then, some asymptotic properties of coexistent solutions induced by the mortality rate, nonlinear growth of predator and cross-diffusion are analyzed. It is revealed that there exist critical values related to certain principal eigenvalues such that the nonlinear growth, cross-diffusion and protection zone all have significant effects on the coexistent solutions; as far as the nonlinear growth concerned, we find that it has important influences on the coexistence region of two species undoubtedly. Biologically, this implies that these critical values greatly affect the survival of species. [ABSTRACT FROM AUTHOR]

Prediabetes is an important stage in the development of diabetes. It is necessary to find a safe, effective and sustainable way to delay and reverse the progression of prediabetes. Akkermansia muciniphila (A. muciniphila) is one of the key bacteria associated with glucose metabolism. Recent studies mainly focus on the effect of A. muciniphila on obesity and insulin resistance, but there is no research on the effect of A. muciniphila on pancreatic β-cell function and its mechanism in prediabetes. In this study, we investigated the effects of A. muciniphila on β-cell function, apoptosis and differentiation, as well as its effects on the gut microbiome, intestinal barrier, metaflammation and the expression of Toll-like receptors (TLRs) in a high-fat diet (HFD)-induced prediabetic rat model. The effect of A. muciniphila was compared with dietary intervention. The results showed both A. muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improve β-cell secretory function, apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4. Additionally, A. muciniphila can further elevate β-cell secretion, attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet. [ABSTRACT FROM AUTHOR]

The thermal conductivity of soil is an essential parameter for designing geothermal energy foundations and borehole heat exchange systems. To effectively improve the development efficiency of geothermal resources in the loess region of China, the plane heat source method was used to measure the thermal conductivity of loess samples with different water contents and temperatures, and scanning electron microscopy tests were conducted. Analyze the effects of water content, temperature, and soil microstructure on thermal conductivity. A weighted geometric mean model considering the soil temperature effect is proposed and compared with the traditional model. The experimental results reveal that soil thermal conductivity increases in stages as the temperature rises. After the temperature exceeds 30℃, the contribution of steam latent heat transfer to soil thermal conductivity gradually becomes significant. Within the temperature range of 1–60℃, the thermal conductivity increases with increasing saturation and tends to stabilize after saturation exceeds 60%; When the temperature is greater than 60℃, the thermal conductivity peaks near a saturation of 60%. As the water content increases, there is a significant difference in the thermal conductivity of undisturbed and remolded loess, which is related to the microstructure changes of the soil. The model calculation shows that the weighted geometric mean model proposed in this paper has the best prediction performance. The Leong model has good predictive performance for the thermal conductivity of loess, while the Gori and Lusen models have the lowest predictive accuracy. [ABSTRACT FROM AUTHOR]

Controlling the content of athermal martensite and retained austenite is important to improving the mechanical properties of high-strength steels, but a mechanism for the accurate description of martensitic transformation during the cooling process must be addressed. At present, frequently used semi-empirical kinetics models suffer from huge errors at the beginning of transformation, and most of them fail to exhibit the sigmoidal shape characteristic of transformation curves. To describe the martensitic transformation process accurately, based on the Magee model, we introduced the changes in the nucleation activation energy of martensite with temperature, which led to the varying nucleation rates of this model during martensitic transformation. According to the calculation results, the relative error of the modified model for the martensitic transformation kinetics curves of Fe–C–X (X = Ni, Cr, Mn, Si) alloys reached 9.5% compared with those measured via the thermal expansion method. The relative error was approximately reduced by two-thirds compared with that of the Magee model. The incorporation of nucleation activation energy into the kinetics model contributes to the improvement of its precision. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the three-dimensional (3D) geometric and electronic structure of molecules play a crucial role in determining their key properties and intermolecular interactions. Therefore, it is necessary to establish a quantum chemical (QC) property database containing the most stable 3D geometric conformations and electronic structures of molecules. In this study, a high-quality QC property database, called QuanDB, was developed, which included structurally diverse molecular entities and featured a user-friendly interface. Currently, QuanDB contains 154,610 compounds sourced from public databases and scientific literature, with 10,125 scaffolds. The elemental composition comprises nine elements: H, C, O, N, P, S, F, Cl, and Br. For each molecule, QuanDB provides 53 global and 5 local QC properties and the most stable 3D conformation. These properties are divided into three categories: geometric structure, electronic structure, and thermodynamics. Geometric structure optimization and single point energy calculation at the theoretical level of B3LYP-D3(BJ)/6-311G(d)/SMD/water and B3LYP-D3(BJ)/def2-TZVP/SMD/water, respectively, were applied to ensure highly accurate calculations of QC properties, with the computational cost exceeding 107 core-hours. QuanDB provides high-value geometric and electronic structure information for use in molecular representation models, which are critical for machine-learning-based molecular design, thereby contributing to a comprehensive description of the chemical compound space. As a new high-quality dataset for QC properties, QuanDB is expected to become a benchmark tool for the training and optimization of machine learning models, thus further advancing the development of novel drugs and materials. QuanDB is freely available, without registration, at https://quandb.cmdrg.com/. Scientific contribution: The QuanDB database contains comprehensive quantum chemical properties of diverse organic molecular entities, and all data have been rigorously pretreated and manually cleaned to ensure high accuracy. By utilizing the quantum chemical properties provided by QuanDB, relevant three-dimensional (3D) electronic structural information can be included in comprehensive molecular representation models to facilitate drug and material design. Compared to other similar databases, QuanDB covers a broader space of chemical compounds, adopts a higher level of theoretical calculations, and offers a user-friendly interface. [ABSTRACT FROM AUTHOR]

The neurological injury and repair mechanisms after ischemic stroke are complex. The inflammatory response is present throughout stroke onset and functional recovery, in which CD4 + T helper(Th) cells play a non-negligible role. Th17 cells, differentiated from CD4 + Th cells, are regulated by various extracellular signals, transcription factors, RNA, and post-translational modifications. Th17 cells specifically produce interleukin-17A(IL-17A), which has been reported to have pro-inflammatory effects in many studies. Recently, experimental researches showed that Th17 cells and IL-17A play an important role in promoting stroke pathogenesis (atherosclerosis), inducing secondary damage after stroke, and regulating post-stroke repair. This makes Th17 and IL-17A a possible target for the treatment of stroke. In this paper, we review the mechanism of action of Th17 cells and IL-17A in ischemic stroke and the progress of research on targeted therapy. [ABSTRACT FROM AUTHOR]

We assessed the situation of endosulfan residues in cotton fields after the endosulfan ban came into effect and the current knowledge, attitude, and practice (KAP) of cotton farmers on the phase-out of endosulfan and the application of alternative technologies. Topsoil samples (n = 91) of cotton fields were collected from the major cotton-producing areas in China, namely the north-west inland cotton region, and the endosulfan residues were analyzed. A KAP survey was carried out for cotton farmers, and 291 questionnaires were distributed. The influences of gender, age, education background, cotton planting years, publicity and training, income sources, and other factors on cotton farmers' KAP were analyzed. The results showed that endosulfan sulfate was the main endosulfan residue in the soil, followed by β-endosulfan and α-endosulfan, the average residual contents were 0.569, 0.139, and 0.060 µg/kg, respectively. The results of the KAP study showed that cotton farmers scored low on knowledge about the phase-out of endosulfan and the application of alternative technologies but high on attitude and practice. The number of family members, years of cotton planting, age, and the cotton-planting area had different degrees of influence on KAP scores. The training could significantly improve the KAP scores of cotton farmers; training should be more targeted and designed reasonably for key groups, such as men and the population under 30, followed by training them to use pesticides safely. For large-scale cotton growers, training should focus on green prevention and control technologies. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the graft outcomes and complications of two endoscopic perichondrium–cartilage graft techniques for repairing large perforations. Study design: Single center blinded randomized controlled trial. Materials and methods: 61 large perforations more than 50% of TM area were prospectively randomized to undergo the free perichondrium and free cartilage graft group (FPFC, n = 31) or perichondrium partial attachment the cartilage graft group (PPAC, n = 30). The primary outcome measures were the operation time; secondary outcome measures were the graft success rate and hearing gain at 12 months postoperatively and postoperative complications. Results: All patients completed follow-up of 12 months. The mean operation time was 38.2 ± 2.3 min in the FPFC group and 37.4 ± 5.6 min in the PPAC group (P = 0.658). At postoperative 3 months, the graft success rates were 96.7% in the FPFC group and 93.3% in the PPAC group (P = 0.976). At postoperative 12 months, the graft success rates were 96.7% in the FPFC group and 83.3% in the PPAC group (P = 0.182). However, the residual and re-perforation rate with no infection was 0.0% (0/31) in the FPFC group and 16.7% (5/30) in the PPAC group (P = 0.056). No significant between-group differences were observed pre- (P = 0.842) or post- (P = 0.759) operative air bone gap (ABG) values or mean ABG gain (P = 0.886). However, granular myringitis has been noted in 6.5% in the FPFC group and in 3.3% in the PPAC group. Conclusions: This study suggested that 12-month graft success and hearing gain were comparable between the perichondrium free and partial attachment the cartilage graft techniques, nevertheless, partial attachment technique could increase residual and re-perforations. [ABSTRACT FROM AUTHOR]

Glycosylation modification of proteins is a common post-translational modification that exists in various organisms and has rich biological functions. It is usually catalyzed by multiple glycosyltransferases located in the Golgi apparatus. β-1,3-N-acetylglucosaminyltransferases (B3GNTs) are members of the glycosyltransferases and have been found to be involved in the occurrence and development of a variety of diseases including autoimmunity diseases, cancers, neurodevelopment, musculoskeletal system, and metabolic diseases. The functions of B3GNTs represent the glycosylation of proteins is a crucial and frequently life-threatening step in progression of most diseases. In this review, we give an overview about the roles of B3GNTs in tumor, nervous system, musculoskeletal and metabolic diseases, describing the recent results about B3GNTs, in order to provide a research direction and exploration value for the prevention, diagnosis and treatment of these diseases. [ABSTRACT FROM AUTHOR]

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research. [ABSTRACT FROM AUTHOR]

Birnessite is regarded as an efficient oxidizing agent that would significantly influence the environmental fate of elements such as arsenic. This study compared the chemical and photocatalytic oxidation of As(III) over birnessite. During the chemical oxidation, As(III) was oxidized to As(V), while Mn(IV) was reduced to Mn(II), subsequently forming MnOOH. The coverage of the reactive sites by MnOOH inhibited the chemical oxidation of residual As(III). At pH 5.0, after 360 min of reaction, 61% of As(III) was oxidized to As(V), and the oxidation of As(III) decreased with an increase in pH. The photocatalytic oxidation of As(III), where almost all As(III) could be oxidized to As(V) over a pH range of 5.0–8.0 and 360 min, was much more efficient compared to chemical oxidation. In contrast to chemical oxidation, the formation of MnOOH slightly affected the photocatalytic performance of birnessite. It was demonstrated that •O2− radicals and holes (hvb+) played an important role in the photocatalytic oxidation of As(III) over birnessite. Our findings confirmed that light dramatically promoted the oxidation of As(III) by birnessite, broadening the understanding of the environmental behaviors of arsenic. [ABSTRACT FROM AUTHOR]

The growth and sustainable development of humanity is heavily dependent upon molecular nitrogen (N2) fixation. Herein we discover ambient catalyst-free disproportionation of N2 by water plasma which occurs via the distinctive HONH-HNOH+• intermediate to yield economically valuable nitroxyl (HNO) and hydroxylamine (NH2OH) products. Calculations suggest that the reaction is prompted by the coordination of electronically excited N2 with water dimer radical cation, (H2O)2+•, in its two-center-three-electron configuration. The reaction products are collected in a 76-needle array discharge reactor with product yields of 1.14 μg cm–2 h–1 for NH2OH and 0.37 μg cm–2 h–1 for HNO. Potential applications of these compounds are demonstrated to make ammonia (for NH2OH), as well as to chemically react and convert cysteine, and serve as a neuroprotective agent (for HNO). The conversion of N2 into HNO and NH2OH by water plasma could offer great profitability and reduction of polluting emissions, thus giving an entirely look and perspectives to the problem of green N2 fixation. The growth and sustainable development of humanity is heavily dependent upon N2 fixation. Herein, authors developed an ambient catalyst-free disproportionation of N2 by water plasma to yield economically valuable nitroxyl and hydroxylamine products. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. Methods: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. Results: Finally, 7803 participants aged 3–18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3–5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. Conclusion: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a common complication of pregnancy and can have significant impact on obstetric and neonatal outcomes. Increasing evidence has shown that the inhibited mechanistic target of rapamycin (mTOR) signaling in placenta is associated with FGR. However, interpretation of existing research is limited due to inconsistent methodologies and varying understanding of the mechanism by which mTOR activity contributes to FGR. Hereby, we have demonstrated that different anatomic regions of human and mouse placentas exhibited different levels of mTOR activity in normal compared to FGR pregnancies. When using the rapamycin-induced FGR mouse model, we found that placentas of FGR pregnancies exhibited abnormal morphological changes and reduced mTOR activity in the decidual-junctional layer. Using transcriptomics and lipidomics, we revealed that lipid and energy metabolism was significantly disrupted in the placentas of FGR mice. Finally, we demonstrated that maternal physical exercise during gestation in our FGR mouse model was associated with increased fetal and placental weight as well as increased placental mTOR activity and lipid metabolism. Collectively, our data indicate that the inhibited placental mTOR signaling contributes to FGR with altered lipid metabolism in mouse placentas, and maternal exercise could be an effective method to reduce the occurrence of FGR or alleviate the adverse outcomes associated with FGR. Human and mouse placentas have different mTOR signaling activities in different anatomic regions in normal and FGR pregnancies. Pregnant mice with FGR induced by rapamycin show smaller placentas, decreased mTOR activity in DJ layer of placenta and altered lipid metabolism. Maternal exercise partially alleviates the abnormal outcomes of FGR model. [ABSTRACT FROM AUTHOR]

Soil thermal conductivity is an important indicator for developing and utilizing geothermal resources. In this study, the impact of underground environmental factors on the thermal conductivity of loess was explored by studying the thermal conductivity of saturated and unsaturated loess under varying water content, dry density, and temperature using the Hot Disk thermal constant analyzer. The results show that the thermal conductivity of unsaturated undisturbed and remolded loess presents different growth trends as the water content increases. When the water content is less than 9%, the thermal conductivity of undisturbed soil increases slowly. The thermal conductivity of unsaturated loess gradually increases with temperature. When the temperature rises above 30°C, the latent heat transfer of steam gradually strengthens, accelerating the increase in thermal conductivity, which is most noticeable at intermediate saturation. However, the thermal conductivity of saturated loess rises slowly as the temperature rises. A weighted geometric average model is proposed in this study to predict the thermal conductivity of loess under temperature conditions, considering the effects of soil water content, dry density, and mineral content. The model accuracy was corroborated by the measured soil thermal conductivity and the data collected from six regions. [ABSTRACT FROM AUTHOR]

Global warming is an irreversible trend. Maize hybrids responded differently to elevated temperature throughout the whole growth periods, but the underlying mechanisms are unclear, particularly from the early stalk growth stage that is used to adapt different environments. For this, two hybrids, Zhengdan958 (heat-tolerant hybrid) and Xianyu335 (heat-sensitive hybrid), including control (CK), the whole growth period increased by 2 °C (CK+2°C), and the whole growth period increased by 4 °C (CK+4°C). Compared to CK, the length of the third internode of CK+2°C and CK+4°C at 56 days after planting (DAP), increased on average by 6.91% and 19.20%, respectively. The elongation of internode in XY335 grew faster than in ZD958, and the third internode density of XY335 decreased more than that of ZD958 at 28 DAP. With temperature increasing, cell length elongated significantly, and cell layers decreased significantly under the CK+4°C and CK+2°C. Compared with CK, the total width of ground tissue cells, hypodermis cells and epidermis cell width of CK+4°C and CK+2°C decreased by 26.16%, 30.29%, 28.82%, and 18.57%, 24.39%, 17.11%, respectively. The major axe (R1), minor axe (R2), and length of the third internode were correlated negatively with ratios of IAA/ABA, ZR/ABA, and GA3/ABA. There was significantly positive relationship between total width of ground tissue cells and crushing strength, thrust resistance (p < 0.05). And the correlations between crushing strength and thrust resistance (p < 0.05), R1 cell layers and R2 cell layers (p < 0.01) was significantly positive. This finding would supply a reference to evolve strategies in breeding stress-tolerant hybrids under the global climate change. [ABSTRACT FROM AUTHOR]

Stock market crashes bring about huge economic loss, so predicting the stock market crashes is extremely important for both the investors and practitioners. Back propagation (BP) neural network performed greatly in data adaptability and fitting, it has been widely used for forecasting study in various fields. However, given the low frequency and lack of periodicity of stock market crashes, the BP neural network can hardly predict the intensively fluctuated stock prices accurately during the crashes. To resolve this issue, we introduced BP neural network into Log-periodic power law model, proposed the Log-periodic power law hybrid model based on the BP neural network. This combined approach could further capture the fluctuation trend and predict the volatility during the stock market crashes better. The experimental results showed that this hybrid model could predict the stock prices in different stock markets with a slightly increased accuracy. Moreover, its performance was more stable compared with BP neural network. [ABSTRACT FROM AUTHOR]

Machine learning models have been widely used in landslide susceptibility prediction. However, landslide multidimensional feature extraction, model generalization ability, and prediction quantification of deep learning are still challenging. This paper proposes a new approach, the landslide density-based bidirectional long short-term memory (LD-BiLSTM) model with multichannel input and an optimized sampling strategy to predict and map landslide susceptibility in active seismic mountainous areas of Sichuan Province, China. First, to ensure the generalization ability of the LD-BiLSTM model, other regions in Sichuan were selected as the model training area independent of the prediction area (Luding County). Multichannel landslide datasets were constructed to extract high-dimensional geospatial features of landslides. Subsequently, the landslide density of each grid cell was utilized as the label for the corresponding input sample. The LD-BiLSTM model was improved by using transfer learning and sampling optimization strategies, which makes our method attenuate the impact of historical landslide inventory deviation on the spatial susceptibility mode compared with the existing DL model, which usually uses landslide objects (LO) as input sample labels. Model performance evaluation results show that the LD-BiLSTM model (precision = 0.903, recall = 0.899, F1-score = 0.901, Area under receiver operating characteristic curve (AUC) = 0.940) outperformed the LO-BiLSTM model (precision = 0.812, recall = 0.815. F1-score = 0.813, AUC = 0.910) in the case areas. Meanwhile, the performance of the LD-BiLSTM model (AUC = 0.9407) significantly outperformed both the information value (IV) (AUC = 0.7207) model and the random forest (RF) (AUC = 0.8116) models in the landslide prediction area (Luding), which confirms that the proposed LD-based method is superior to traditional LO-based methods. Significantly, our approach can effectively extract the spatial distribution of landslides and predict potential landslides in complex high-mountain environments. [ABSTRACT FROM AUTHOR]

Purpose: To describe the association of refraction development and axial length (AL) in young children and provide new insights into the progression of cylinder power. Methods: Children (2–3 grades) were enrolled from primary schools in Shanghai and followed up for two years. Cycloplegic refraction, AL, and corneal curvature radius were measured. Refraction parameters were compared among groups with different AL, AL1 (AL < 23.5 mm), AL2 (23.5 mm ≤ AL < 24.5 mm), and AL3 (AL ≥ 24.5 mm). Multiple regression analysis was used to explore risk factors of diopter of cylinder (DC) progression. Results: In total, out of 6891 enrolled children, 5961 participants (7–11 yrs) were included in the final analysis. Over the two-year period, the cylinder power significantly changed, and those with longer AL had more rapid DC progression over the two years (AL1, -0.09 ± 0.35 D; AL2, -0.15 ± 0.39 D; AL3, -0.29 ± 0.44 D) (P < 0.001). The change in DC was independently associated with AL at baseline (P < 0.001). The proportion of with-the-rule astigmatism increased from 91.3% to 92.1% in AL1 group, from 89.1% to 91.8% in AL2 group and from 87.1% to 92.0% in AL3 group. Conclusions: Young children with long AL experienced rapid progression of cylinder power. Both the control of myopia progression and attention to the correction of astigmatism are necessary in the health management of children with long AL. The significantly increased AL in participants might contribute to both the extent and direction of astigmatism. [ABSTRACT FROM AUTHOR]

The integral development of agriculture and tourism heavily depends on natural resources, especially agricultural resources, and it also may contribute to the sustainability of agriculture. The sustainability of agriculture is usually measured by the agricultural eco-efficiency. The main objective of this paper is to demonstrate the impact of the agriculture and tourism integration on agricultural eco-efficiency, so as to reflect the role of the agriculture and tourism integration on promoting agricultural sustainability. Applying panel data of 19 provinces in Yangtze River Basin and Yellow River Basin in China from 2008 to 2019, this paper uses a PSTR model to demonstrate the impact of agriculture and tourism integration on agricultural eco-efficiency and its mechanisms. It is found that in the study area, the integration of agriculture and tourism can contribute to improvements in agricultural eco-efficiency, and when levels of integration are high, the promotional effect is enhanced. However, impacts vary among different regions to some extent. In terms of influencing mechanisms, inputs of agricultural labor, sown crop area, effective irrigation area and other factors decrease with continuous improvements of integration. The input of pesticides, fertilizers and other factors does not decrease in the initial stage of integration but undergoes a rapid decrease after crossing a threshold value. And it demonstrates that the integration of agriculture and tourism is beneficial for improving the agricultural eco-efficiency, so that it will contribute to agricultural sustainability. Meanwhile, this paper offers a new research perspective for discovering effects of agriculture and tourism integration, providing implications for formulating regional policies for the integration. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop and validate an ultrasound (US)-based nomogram for the preoperative differentiation of renal urothelial carcinoma (rUC) from central renal cell carcinoma (c-RCC). Methods: Clinical data and US images of 655 patients with 655 histologically confirmed malignant renal tumors (521 c-RCCs and 134 rUCs) were collected and divided into training (n = 455) and validation (n = 200) cohorts according to examination dates. Conventional US and contrast-enhanced US (CEUS) tumor features were analyzed to determine those that could discriminate rUC from c-RCC. Least absolute shrinkage and selection operator regression was applied to screen clinical and US features for the differentiation of rUC from c-RCC. Using multivariate logistic regression analysis, a diagnostic model of rUC was constructed and visualized as a nomogram. The diagnostic model’s performance was assessed in the training and validation cohorts by calculating the area under the receiver operating characteristic curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness of the US-based nomogram. Results: Seven features of both clinical features and ultrasound imaging were selected to build the diagnostic model. The nomogram achieved favorable discrimination in the training (AUC = 0.996, 95% CI: 0.993–0.999) and validation (AUC = 0.995, 95% CI: 0.974, 1.000) cohorts, and good calibration (Brier scores: 0.019 and 0.016, respectively). DCA demonstrated the clinical usefulness of the US-based nomogram. Conclusion: A noninvasive clinical and US-based nomogram combining conventional US and CEUS features possesses good predictive value for differentiating rUC from c-RCC. [ABSTRACT FROM AUTHOR]

Microbial C use efficiency (CUE) and turnover are critical to driving the global C cycle because they regulate C flux between soil and atmosphere. However, the elevational patterns of microbial CUE and turnover are still unclear. This study investigated microbial growth, respiration, biomass turnover time, and CUE at two soil depths (0–20 cm and 20–40 cm) across nine sites along an elevational gradient from 864 to 2856 m in a subtropical forest using an 18O-H2O-DNA approach. Microbial CUE increased with elevation in subsoil (20–40 cm), while it was not affected by elevation in topsoil (0–20 cm), and the increasing CUE with elevation was more related to microbial growth rather than respiration. Microbial growth normalized to MBC (qGrowth) increased with elevation, while microbial biomass turnover time decreased, and microbial respiration normalized to MBC (qCO2) was stable with elevation. Soil pH was negatively related to microbial CUE in topsoil and explained the most elevational variation of CUE. Differently, C:N stoichiometric imbalance between soil and microorganisms determined microbial CUE in subsoil. Altogether, our study provides strong evidence that the elevational pattern and driving factors of microbial CUE vary with soil depth, which may improve our understanding of C cycling and sequestration in the subtropical forest soil. [ABSTRACT FROM AUTHOR]

The task offloading of mobile edge computing (MEC) is to find proper edge or cloud resources for the execution tasks to efficiently utilize resources and meet different user's requirements. However, it is difficult for task offloading when the number of tasks and resources providers increases and to optimize multiple objectives while satisfying users' requirements. In this paper, a new multi-objective strategy based on the biogeography-based optimization (BBO) algorithm is proposed for MEC offloading to satisfied users' multiple requirements (the execution time, energy consumption and cost). In this strategy, a time-energy consumption model and a cost model are constructed for task offloading firstly. Based on these models, the BBO algorithm is introduced into task offloading for MEC to solve the problem of multi-objective optimization. Compared with the traditional strategies, the offloading strategy based on BBO decreases the average task completion time by an average of 25.03%, and compared with the technique for order preference by similarity to an ideal solution (TOPSIS) strategy, the BBO offloading strategy proposed in this paper reduces energy consumption 75% and cost by 36.9%. The proposed strategy can well solve the problem of multi-objective optimization in the task offloading for MEC. [ABSTRACT FROM AUTHOR]

Background: Additional immunotherapies are still warranted for non-responders to checkpoint inhibitors with refractory or relapsing cancers, especially for patients with "cold" tumours lacking significant immune infiltration at treatment onset. We developed XFab-α4-1BB/CD40L, a bispecific antibody targeting 4-1BB and CD40 for dendritic cell activation and priming of tumour-reactive T cells to inhibit tumours. Methods: XFab-α4-1BB/CD40L was developed by engineering an anti-4-1BB Fab arm into a CD40L trimer based on XFab® platform. Characterisation of the bispecific antibody was performed by cell-based reporter assays, maturation of dendritic cell assays, and mixed lymphocyte reactions. The abilities of antigen-specific T-cell expansion and antitumour efficacy were assessed in syngeneic mouse tumour models. Toxicological and pharmacodynamic profiles were investigated in non-human primates. Results: XFab-α4-1BB/CD40L demonstrated independent CD40 agonistic activity and conditional 4-1BB activity mediated by CD40 crosslinking, leading to dendritic cell maturation and T-cell proliferation in vitro. We confirmed the expansion of antigen-specific T cells in the vaccination model and potent tumour regression induced by the bispecific antibody alone or in combination with gemcitabine in vivo, concomitant with improved tumour-reactive T-cell infiltration. XFab-α4-1BB/CD40L showed no signs of liver toxicity at doses up to 51 mg/kg in a repeated-dose regimen in non-human primates. Conclusions: XFab-α4-1BB/CD40L is capable of enhancing antitumour immunity by modulating dendritic cell and T-cell functions via targeting 4-1BB agonism to areas of CD40 expression. The focused, potent, and safe immune response induced by the bispecific antibody supports further clinical investigations for the treatment of solid tumours. [ABSTRACT FROM AUTHOR]