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LSD1 (histone lysine-specific demethylase 1) has been gradually disclosed to act as an immunomodulator to enhance antitumor immune response. Despite the identification of numerous potent LSD1 inhibitors, there remains a lack of LSD1 inhibitors approved for marketing. Novel LSD1 inhibitors with different mechanisms are therefore needed. Herein, we reported a series of novel quinazoline-based LSD1 inhibitors. Among them, compound Z-1 exhibited the best LSD1 inhibitory activity (IC50= 0.108 μM). Z-1 also acted as a selective and cellular active as an LSD1 inhibitor. Furthermore, Z-1 promoted response of gastric cancer cells to T-cell killing effect by decreasing PD-L1 expression and further attenuated the PD-1/PD-L1 interaction. In vivo, Z-1 exhibited significant suppression effect on the growth of gastric cancer cells without obvious toxicity. Therefore, Z-1 represents a potential novel immunomodulator that targets LSD1, providing a lead compound with new function mechanism for gastric cancer treatment.

A zinc-organic hybrid (1) with multifunctional room temperature phosphorescence (RTP) was synthesized. 1presents light/force-sensitive RTP properties due to the photochromic behavior from gray to light yellow and the transition from crystalline to amorphous state, respectively. Furthermore, inkless printing and information encryption models were successfully constructed to prove their widespread application prospect.

A 3D interconnected MOF framework is rationally designed by a universal polydopamine-engineered “double-sided tape” strategy, which offers continuous and short-range Li+pathways to realize fast Li+transport within all-solid-state electrolytes.

Camptothecin (CPT) exhibits potent antitumor activity; however, its clinical application is limited by significant gastrointestinal adverse effects (GAEs). Although the severity of GAEs associated with CPT derivatives has decreased, the incidence rate of these adverse effects has remained high. CPT multifunctional nanoparticles (PCRHNs) have the potential to increase the efficacy of CPT while reducing side effects in major target organs; however, the impact of PCRHNs on the GAEs from CPT remains uncertain. Here, we investigated the therapeutic effects of PCRHNs and different doses of CPT and examined their impacts on the intestinal barrier and the intestinal microbiota. We found that the therapeutic efficacy of PCRHNs + Laser treatment was superior to that of high-dose CPT, and PCRHNs + Laser treatment also provided greater benefits by helping maintain intestinal barrier integrity, intestinal microbiota diversity, and intestinal microbiota abundance. In summary, compared to high-dose CPT treatment, PCRHNs + Laser treatment can effectively balance therapeutic effects and GAEs. A high dose of CPT promotes the enrichment of the pathogenic bacteria Escherichia-Shigella, which may be attributed to diarrhea caused by CPT, thus leading to a reduction in microbial burden; additionally, Escherichia-Shigellarapidly grows and occupies niches previously occupied by other bacteria that are lost due to diarrhea. PCRHNs + Laser treatment increased the abundance of Lactobacillus(probiotics), possibly due to the photothermal effect of the PCRHNs. This effect increased catalase activity, thus facilitating the conversion of hydrogen peroxide into oxygen within tumors and increasing oxygen levels in the body, which is conducive to the growth of facultative anaerobic bacteria.

Titanium matrix composites reinforced with ceramic particles are considered a promising engineering material due to their combination of high specific strength, low density, and high modulus. In this study, the TA15-based composites reinforced with a volume fraction of 10% to 25% (TiB+TiC) were prepared using powder metallurgy and casting technique. Microstructural characterization and phase constitution were examined using optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In addition, the microhardness, room temperature (RT) and high temperature (HT) tensile properties of the composites were evaluated. Results revealed that the reinforcements are distributed uniformly even in the composites with a high volume of TiB and TiC. However, as the volume fraction exceeds 15%, TiB and TiC particles become coarsening and exhibit rod-like and dendritic-like morphology. Microhardness increases gradually from 321.2 HV for the base alloy to a maximum of 473.3 HV as the reinforcement increases to 25vol.%. Tensile test results indicate that a reinforcement volume fraction above 20% is beneficial for enhancing tensile strength and yield strength at high temperatures, but it has an adverse effect on room temperature elongation. Conversely, if the reinforcement volume fraction is below 20%, it can improve high-temperature elongation when the temperature exceeds 600 °C.

In this paper, the Fe/Si reduction efficiency, Gd/Mn alloying efficiency, and corrosion susceptibility of the Mg-xMn-4.0Gd alloy were investigated. The results reveal that adding Mn gives a more prominent Fe removal effect under the conventional smelting processes. Neither the amount of Gd addition nor excessive Mn addition is sufficient for the continued strengthening of the Fe removal effect. The alloying efficiency of Mn increased and then decreased as a result of adding Mn alone to mixtures of Mn and Gd elements, while the alloying efficiency of Gd elements gradually diminished. An appropriate amount of Mn addition is beneficial for efficiently improving the corrosion resistance of the alloy. The extruded Mg-0.8Mn-4.0Gd alloy has more outstanding corrosion resistance, with a CRWeighet Lossof 4.48 ± 0.33 mg/(cm2·d) and CRHydrogen Evolutionof 2.01 ± 0.31 ml/(cm2·d). The corrosion susceptibility of the extruded Mg-xMn-4.0Gd alloy mainly hinges on the grain size, Gd solid solubility, and texture intensity of basal plane I(0002).

The relationships between the selective laser melting (SLM) processing parameters including laser power, scanning speed and hatch space, the relative density, the microstructure, and resulting mechanical properties of Ti-6Al-2Zr-1Mo-1V alloy were investigated in this work. The result shows that laser power acts a dominant role in determining the relative density in comparison with scanning speed and hatch space. The optimal SLM process window for fabricating relative density >99% samples is located in the energy density range of 34.72 J·mm−3to 52.08 J·mm−3, where the laser power range is between 125 W and 175 W. An upward trend is found in the micro-hardness as the energy density is increased. The optimum SLM processing parameters of Ti-6Al-2Zr-1Mo-1V alloy are: laser power of 150 W, scanning speed of 1,600 mm·s−1, hatch space of 0.08 mm, and layer thickness of 0.03 mm. The highest ultimate tensile strength, yield strength, and ductility under the optimum processing parameter are achieved, which are 1,205 MPa, 1,099 MPa, and 8%, respectively. The results of this study can be used to guide SLM production Ti-6Al-2Zr-1Mo-1V alloy parts.

Hot temperature extremes (HTEs) in the atmosphere can also affect lake surface water temperature, but how this impact changes with global warming is not well understood. Here we use numerical modelling and satellite observations to quantify the contribution of HTEs to variations in summer lake surface water temperature and lake heatwaves in 1,260 water bodies worldwide between 1979 and 2022. Over this time period, HTE duration and cumulative intensity over the studied lakes increased significantly, at average rates of 1.4 days per decade and 0.92 °C days per decade, respectively. Despite only accounting for 7% of the total summer days, HTEs are responsible for 24% of lake surface summer warming trends, with the most pronounced effect observed in Europe at 27%. Moreover, HTEs are key drivers of both the duration and cumulative intensity of lake heatwaves. Our findings underscore the pivotal role played by short-term climatic extreme events in shaping long-term lake surface water temperature dynamics.

Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosisby inhibiting ATP synthase1,2. However, BDQ also inhibits human ATP synthase3. At present, how these compounds interact with either M. tuberculosisATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosisATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosisATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosisATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers’ understanding of the similarities and differences between human ATP synthase and M. tuberculosisATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.

Bruce llosis is a bacterial disease caused by various Brucella species, which infect primarily cattle, swine, goats, sheep, and dogs. The disease is typically transmitted to humans through direct contact with diseased animals, consumption of contaminated animal products, or inhalation of airborne pollutants. The majority of cases are caused by consuming unpasteurized goat or sheep milk or cheese. Based on observed Brucellosis occurrence data and ecogeographic variables, a MaxEnt algorithm was used to model the current and future distribution of Brucellosis in Qinghai Lake basin, P.R. China. Our model showed the Brucellosis current distribution and predicts suitable habitat shifts under future climate scenarios. In the new representatives; SSP 2.6 and SSP 4.5 for the year 2050s and 2070s, our model predicts an expansion in the current suitable areas. This indicates that under the possible climate changes in the future, the living space of Brucellosis in Qinghai Lake basin China will expand significantly. Ecogeographic variables that contributed significantly to the distribution of Brucellosis in Qinghai Lake basin are revealed by our model. The results of our study will promote comparisons with future research and provide a new perspective to inform decision-making in the field of public health in Qinghai province.

A novel Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy was designed using the cluster formula approach (cluster-plus-glue-atom model) and prepared by laser melting deposition (LMD). Its composition formula 12[Al-Ti12](AlTi2)+5[Al0.8Si0.2-Ti12Zr2](V0.8Mo0.2Nb1Ti) features an enhanced β-Ti via co-alloying of Zr, V, Mo, Nb and Si. The experimental results show that the cluster formula of α and β phases in the novel alloy are respectively α-[Al-Ti11.5Zr0.5](Al1Ti2) and β-[Al0.8Si0.2-Ti13.2Zr0.8](V1Mo0.4Nb1.6), both containing Zr elements. The fitted composition via the α and β phase cluster formulas has little difference with the actual alloy composition, suggesting that the validity of cluster-plus-glue-atom model in the alloy composition design. After hot isostatic pressing (HIP), both the Ti-6Al-4V and the novel alloy by LMD are characterized by prior-β columnar grains, while the typical <100> texture disappears. Compared with Ti-6Al-4V, Ti-5.55Al-6.70Zr-1.50V-0.70Mo-3.41Nb-0.21Si alloy exhibits a combination of higher strength (1,056 MPa) and higher ductility (14%) at room temperature and higher strength (580 MPa) at 550 °C after HIP, and can potentially serves as LMD materials.

Gait disturbances are among the main symptoms of Parkinson’s disease (PD) and can increase fall risk. In this study we aimed to systematically evaluate the effects of different exercise modes on gait indexes of PD patients. We conducted a review and network meta-analysis of randomized controlled trials in studies listed in Web of Science, MEDLINE, EMBASE, PsycINFO, Cochrane Library, ClinicalTrailS.gov, and China National Knowledge Infrastructure databases from their inception to October 23, 2021. Eligible studies were randomized controlled trials investigating the effect of exercise on gait index by using the Timed Up and Go test, (TUG), stride length, stride cadence, or 6 Minutes Walking Test (6MWT). We used Review Manager 5.3 to evaluate the quality of the included literature, and we used Stata 15.1 and R-Studio for the network meta-analysis. We assessed the relative ranking of therapies by the surface under the cumulative ranking possibilities. In 159 studies, there were 24 exercise interventions. Compared with the control group, 13 exercises showed significant improvements on the TUG; six exercises were significantly better for improving stride length; only one exercise was better for improving stride cadence; and four exercises were better for improving the 6MWT. The surface under the cumulative ranking curves suggested that Pilates, body weight support treadmill training, resistance training, and a multidisciplinary exercise program were preferable for gains on TUG, stride length, stride cadence, and 6MWT. This meta-analytic review found that exercise therapies bring obvious benefits to gait indexes of patients with PD, and the efficacy of exercise therapies varied with different types of exercise and outcome indexes.

This article presents several actuarial applications of categorical embedding in the context of non-life insurance risk classification. In non-life insurance, many rating factors are naturally categorical, and often the categorical variables have a large number of levels. The high cardinality of categorical rating variables presents challenges in the implementation of traditional actuarial methods. Categorical embedding that is proposed in the machine learning literature for handling categorical variables has recently received attention in actuarial studies. The method is inspired by the neural network language models for learning text data and maps a categorical variable into a real-valued representation in the Euclidean space. Using a property insurance claims we demonstrate the use of categorical embedding in three applications. The first shows how embeddings are used to construct rating classes and calculate rating relativities for a single insurance risk. The second concerns predictive modeling for multivariate insurance risks and emphasizes the effects of dependence on tail risks. The third focuses on pricing new products where transfer learning is used to gather knowledge from existing products.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU + DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU + DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU + DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.

The associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties.

Dynamic path planning for mobile robots is an urgent issue that needs to be solved because of the growing use of mobile robots in daily life and industrial operations. This work focuses on avoiding moving obstacles in dynamic situations. The computational effort required by some current algorithms makes them difficult to utilize for path planning in dynamic situations whilst the computational effort required by other methods makes them simple yet prone to local minima. In this paper, an improved simulated annealing (SA) algorithm for dynamic path planning is proposed. To reduce its computational effort, the initial path selection method and deletion operation are introduced. Simulation results show the improved SA algorithm outperforms other algorithms and provides optimal solutions in static and dynamic environments. [ABSTRACT FROM AUTHOR]

Histone lysine specific demethylase 1 (LSD1) has been recognized as an important epigenetic target for cancer treatment. Although several LSD1 inhibitors have entered clinical trials, the discovery of novel potent LSD1 inhibitors remains a challenge. In this study, the antipsychotic drug chlorpromazine was characterized as an LSD1 inhibitor (IC50= 5.135 μM), and a series of chlorpromazine derivatives were synthesized. Among them, compound 3s(IC50= 0.247 μM) was the most potent one. More importantly, compound 3sinhibited LSD1 in the cellular level and downregulated the expression of programmed cell death-ligand 1 (PD-L1) in BGC-823 and MFC cells to enhance T-cell killing response. An in vivostudy confirmed that compound 3scan inhibit MFC cell proliferation without significant toxicity in immunocompetent mice. Taken together, our findings indicated that the novel LSD1 inhibitor 3stethering a phenothiazine scaffold may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.

Metal- and oxidant-free alkenyl C–H thiolation enabled by the azo group had been established for the modular synthesis of tetrasubstituted acyclic olefins. The reaction was performed under mild reaction conditions with a broad substrate scope. The intramolecular 6-membered hydrogen-bonding network accounts for the observed excellent stereo-control.

In this study, a novel artificial intervertebral disc implant with modified “Bucklicrystal” structure was designed and 3D printed using thermoplastic polyurethane. The new implant has a unique auxetic structure with building blocks joined “face-to-face”. The accompanied negative Poisson’s ratio enables its excellent energy absorption and stability under compression. The deformation and load distribution behavior of the implant under various loading conditions (bending, torsion, extension and flexion) has been thoroughly evaluated through finite element method. Results show that, compared to natural intervertebral disc and conventional 3D implant, our new implant exhibits more effective stress transfer and attenuation under practical loading conditions. The implant's ability to contract laterally under compression can be potentially used to alleviate the symptoms of lumbar disc herniation. Finally, the biocompatibility of the implant was assessed in vitroand its ability to restore the physiological function of the disc segment was validated in vivousing an animal model.

Myocardial infarction (MI) leads to massive cardiomyocyte death and deposition of collagen fibers. This fibrous tissue disrupts electrical signaling in the myocardium, leading to cardiac systolic and diastolic dysfunction, as well as arrhythmias. Conductive hydrogels are a promising therapeutic strategy for MI. Here, we prepared a highly water-soluble conductive material (GP) by grafting polypyrrole (PPy) onto non-conductive gelatin. This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum (OXG) and gelatin to construct an injectable conductive hydrogel. The prepared self-healing OGGP3 (3 wt% GP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the natural heart. The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI. We found that the cardiac function of the rats treated with OGGP3 was improved, making it more difficult to induce arrhythmias. The electrical resistivity of myocardial fibrous tissue was reduced, and the conduction velocity of myocardial tissue was increased. Histological analysis showed reduced infarct size, increased left ventricular wall thickness, increased vessel density, and decreased inflammatory response in the infarcted area. Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation, thus showing its potential for the treatment of MI.

Hot isostatic pressing parameters are critical to Ti60 high temperature titanium alloy castings which have wide application perspective in aerospace. In order to obtain optimal processing parameters, the effects of hot isostatic pressing parameters on defects, composition uniformity, microstructure and mechanical properties of Ti60 cast high temperature titanium alloy were investigated in detail. Results show that increasing temperature and pressure of hot isostatic pressing can reduce defects, especially, the internal defects are substantially eliminated when the temperature exceeds 920 °C or the pressure exceeds 125 MPa. The higher temperature and pressure can improve the microstructure uniformity. Besides, the higher pressure can promote the composition uniformity. With the temperature increases from 880 °C to 960 °C, α-laths are coarsened. But with increasing pressure, the grain size of prior-β phase, the widths of α-laths and α-colony are reduced. The tensile strength of Ti60 alloy is 949 MPa, yield strength is 827 MPa, and the elongation is 11% when the hot isostatic pressing parameters are 960 °C/125 MPa/2 h, which exhibits the best match between the strength and plasticity.

The in situ (TiC+TiB)/TA15 composites with different volume percentages of reinforcement (10%, 15%, 20% and 25%) were prepared by water-cooled copper crucible vacuum suspension melting technology. The structures and compositions of the TA15 alloy and its composites were analyzed by XRD and EDS, and their electrochemical corrosion behavior in the 3.5% NaCl solution was studied. Corrosion wear testing was conducted using a reciprocating ball-on-disc wear tester under a 10 N load. Results show that the in situ fibrous TiB phase and the granular TiC phase are uniformly distributed on the composite matrix. The microhardness can reach up to 531 HV as 10vol.% TiC+TiB reinforcement is added. Compared with the TA15 alloy, the volume wear rate decreases from (2.21±0.07)×10−4to (1.75±0.07)×10−4mm3·N−1·m−1by adding 15vol.% TiC+TiB reinforcement, and the wear mechanism is adhesive wear. When the volume percentage of the reinforcement phase reaches 25%, the volume wear rate increases from (1.75±0.07)×10−4to (2.41±0.07)·10−4mm3·N−1·m−1, and the wear mechanism changes into abrasive wear. The volume loss resulted by the interaction between corrosion and wear accounts for more than 27% of the total wear volume. The volume loss due to wear-induced corrosion changes from 1.94% to 4.06% with different addition of reinforcement. The volume loss caused by corrosion-induced wear initially increases from 24.08% to 26.90% as the reinforcement increases from 0 to 15% due to the increase of corrosion potential, and then decreases from 26.90% to 25.68% as the reinforcement increases from 15% to 25% due to the peeling of TiC phase.

Human-wildlife conflict (HWC) negatively impacts both humans and wildlife. Attitudes of local residents have been critical in promoting wildlife conservation. It is therefore necessary to understand the characteristics of HWC and identify influential factors on attitudes towards conservation to implement conservation strategies efficiently. This research focused on features of human-elephant interactions, while attitudes and values regarding the small population of Asian elephants (Elephas maximus) in Nangunhe National Nature Reserve (NNR), Yunnan, China. The total of 327 valid questionnaires were gathered around the area where Asian elephants were distributed. Logistic regression models were employed to analyze the correlations among five predictor variables (‘Area’, ‘Family size’, ‘Annual income’, ‘Quantity of family members in non-primary industries’ and ‘Experiencing loss or not’) and three response variables (‘Attitude towards elephants’, ‘Perception of the values of elephants’ and ‘Attitude towards tourism development’). The study area was densely forested with tea plants, rubber trees, corns and sugarcane. There, 25.99% of respondents reported the experience of human-elephant conflict (HEC), with crop raiding and cash crop damages being the major conflict types. To demonstrate respect for elephants and to mitigate HEC, a unique custom called ‘Giving tribute to elephants’ was developed long ago. Respondents’ township with an official annual festival of ‘Giving Tribute to Elephants’ (odds ratio (OR) = 2.75, P= 1.73 × 10−6) and higher annual income (OR = 2.09, P= 5.45 × 10−5) significantly contributed to forming a more positive attitude towards elephants, whereas HEC itself have contributed to a more negative attitude (OR = 0.50, P= 3.29 × 10−3). Therefore, we propose that: 1) reducing human-elephant conflict by testing multiple mitigation measures and adopting the most effective one of them; 2) enhancing local livelihoods through the development of ecological products and ecotourism; and 3) preserving and developing the Wa culture in this region. The study area deserves more attention and further research to explore and obtain endorsement from the public to achieve coexistence between human and wildlife.

ABSTRACTSecchi disk depth (SDD) is a simple but particularly important indicator for characterizing the overall water quality status and assessing the long-term dynamics of water quality for diverse global waters. For this reason, countless efforts have been made to collect SDD data from the field and through remote sensing systems. Many empirical and semianalytical algorithms have been proposed to estimate SDD from different satellite images for a specific or regional water. However, the construction of a robust global SDD estimation model is still challenging due to the nonlinear response of SDD to optical properties and the complex physical and biogeochemical processes of different waters. Therefore, machine learning methods to better interpret nonlinear processes were used to improve remote sensing estimations of SDD for global lakes and reservoirs based on a global matchup dataset from Landsat TM (N= 4099), ETM+ (N= 2420), and OLI (N= 1249) covering in situSDD from 0.01 m to over 18 m. Overall, extreme gradient boosting (XGBoost) and random forest (RF) had better SDD retrievals than back propagation neural network, support vector regression, empirical and quasi-analytical models showing high precision with mean relative error of approximately 30% and good agreements with the long-term in situSDD in different waters with various optical properties. Our results can support long-term global-level water quality evaluation and thus making informed decisions about development policy.

Recapitulating inherent heterogeneity and complex microarchitectures within confined print volumes for developing implantable constructs that could maintain their structure in vivohas remained challenging. Here, we present a combinational multimaterial and embedded bioprinting approach to fabricate complex tissue constructs that can be implanted postprinting and retain their three-dimensional (3D) shape in vivo. The microfluidics-based single nozzle printhead with computer-controlled pneumatic pressure valves enables laminar flow-based voxelation of up to seven individual bioinks with rapid switching between various bioinks that can solve alignment issues generated during switching multiple nozzles. To improve the spatial organization of various bioinks, printing fidelity with the z-direction, and printing speed, self-healing and biodegradable colloidal gels as support baths are introduced to build complex geometries. Furthermore, the colloidal gels provide suitable microenvironments like native extracellular matrices (ECMs) for achieving cell growths and fast host cell invasion via interconnected microporous networks in vitroand in vivo. Multicompartment microfibers (i.e., solid, core–shell, or donut shape), composed of two different bioink fractions with various lengths or their intravolume space filled by two, four, and six bioink fractions, are successfully printed in the ECM-like support bath. We also print various acellular complex geometries such as pyramids, spirals, and perfusable branched/linear vessels. Successful fabrication of vascularized liver and skeletal muscle tissue constructs show albumin secretion and bundled muscle mimic fibers, respectively. The interconnected microporous networks of colloidal gels result in maintaining printed complex geometries while enabling rapid cell infiltration, in vivo.

High-entropy alloys (HEAs) are based on solid solutions which characterized by chemical short-range ordering (CSRO), but there is no accurate structural tool to address CSRO characteristic, which obstacles precise composition design for HEAs. In this study, based on the cluster-plus-glue-atoms model, the composition law of Al-TMs (TMs, transition metals) HEAs with BCC and FCC structures was revealed. In BCC structure, with five elements in equi-atomic ratio, the composition formula of Al-TMs HEAs can be expressed by a cluster formula [Al-M14]Al3, and in non equi-atomic ratio can be expressed by [Al-M14]Al, where M is the average atom of the TMs. But in FCC structure, both Al-TMs HEAs with five elements in equi-atomic and non equi-atomic ratios can be expressed by a cluster formula [Al-M12]Al. To confirm the effectiveness of cluster formula for Al-TMs, two alloys were designed, [Al-Ti4V3Nb4Mo3]Mo and [Al-Ti3V3Nb4Mo4]Al. Results show that the [Al-Ti3V3Nb4Mo4]Al alloy has both higher strength and higher plastic deformation at room temperature. Besides, [Al-Ti3V3Nb4Mo4]Al alloy shows slower soften effect at 800 °C, contributed to its higher strength. By substituting Ta for some of Mo, the strength of [Al-Ti3V3Nb4Mo3Ta]Al at room temperature and high temperature drastically decreases, suggesting that Ta element deteriorates the properties of Al-TMs alloys.

Epithelial ovarian cancer (EOC) is the deadliest women’s cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection.

Objective:This study was designed to evaluate the association between macrophage migration inhibitory factor (MIF) gene polymorphisms, serum MIF levels and tuberculosis (TB) susceptibility.Methods:All satisfactory studies were included; the MIFgenotype number and serum MIF levels were reviewed. The Stata and Review Manager software were used for the pooled analyses.Results:The pooled analyses showed that theMIF-173G/C gene polymorphism was associated with TB (allele C vs allele G: odds ratio (OR) = 1.44, 95% confidence interval (CI): 1.28–1.62, p< 0.01; genotype CC vs genotype GG: OR = 1.69, 95% CI: 1.05–2.73, p= 0.03; genotype CC+GC vs genotype GG: OR = 1.56, 95% CI: 1.34–1.81, p< 0.01; genotype GC vs genotype GG: OR = 1.50, 95% CI: 1.28–1.75, p< 0.01). The subgroup analysis showed that the MIF-173G/C gene polymorphism was significantly associated with the risk of both pulmonary tuberculosis (PTB) and spinal tuberculosis (STB).TheMIFCATT-794 gene polymorphism was associated with the PTB susceptibility in Asian subjects (genotypes 5/X+6/X vs genotypes 7/X+8/X: OR = 0.39, 95% CI: 0.24–0.64, p< 0.01; genotypes 5 + 6 vs genotypes 7 + 8: OR = 0.57, 95% CI: 0.48–0.69, p< 0.01). Both PTB and STB patients had significantly elevated serum MIF levels compared to healthy controls.Conclusion:The MIF-173G/C gene polymorphism is related to both PTB and STB susceptibility in both Asian and Caucasian populations. The C allele and CC genotype of the MIF-173G/C SNP appear to be TB risk factors. The MIFCATT-794 gene polymorphism is associated with the PTB susceptibility in Asian subjects; serum MIF levels were significantly increased in PTB and STB patients.

Active metal ions often show a strong cutting effect on the chemical bonds during high-temperature thermal processes. Herein, a one-pot metal ion cutting-assisted method was adopted to design defect-rich MoS2–xnanosheet (NS)/ZnS nanoparticle (NP) heterojunction composites on carbon nanofiber skeletons (CNF@MoS2–x/ZnS) via a simple Ar-ambience annealing. Results show that Zn2+ions capture S2–ions from MoS2and form into ZnS NPs, and the MoS2NSs lose S2–ions and become MoS2–xones. As sulfur hosts for lithium–sulfur batteries (LSBs), the CNF@MoS2–x/ZnS–S cathodes deliver a high reversible capacity of 1233 mA h g–1at 0.1 C and keep 944 mA h g–1at 3 C. Moreover, the cathodes also show an extremely low decay rate of 0.012% for 900 cycles at 2 C. Series of analysis indicate that the MoS2–xNSs significantly improve the chemisorption and catalyze the kinetic process of redox reactions of lithium polysulfides, and the heterojunctions between MoS2–xNSs and ZnS NPs further accelerate the transport of electrons and the diffusion of Li+ions. Besides, the CNF@MoS2–x/ZnS–S LSBs also show an ultralow self-discharge rate of 1.1% in voltage. This research would give some new insights for the design of defect-rich electrode materials for high-performance energy storage devices.

The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk.

The umpolung activity of hemiacetals serving as α-carbon nucleophiles has been reported via dinuclear zinc cooperative catalysis. This umpolung strategy has been applied to catalytic asymmetric tandem reactions of 1-tosylindoline-2,3-diols with β,γ-unsaturated-α-keto compounds, providing a broad series of structurally diverse tetrahydrofuran spirooxindoles and dihydrofurans, respectively. In addition, products could be transformed to quinazoline and quinoline derivatives.

Background:This study was designed to evaluate the influence of vitamin D receptor (VDR) gene polymorphisms on systemic lupus erythematosus (SLE) susceptibility.Methods:All eligible investigations were identified, the number of the various genotypes in the case and control groups were reviewed. A pooled analysis was performed using the Stata software. The study was carried out according to the Ethics Review Committee of The Third Xiangya Hospital, Central South University.Results:This meta-analysis included 19 studies. In our analysis, the VDR Apal polymorphism was correlated with SLE susceptibility in the overall population (AA vs. aa: odds ratio [OR] = 1.374, 95% confidence interval [CI]: 1.115–1.692, p= 0.003; AA + Aa vs. aa: OR = 1.342, 95% CI: 1.139–1.583, p< 0.01). The VDR Bsml and Apal polymorphisms were correlated with SLE susceptibility in Caucasian subjects (BB vs. Bb + bb: OR = 0.734, 95% CI: 0.593–0.909, p= 0.005; B vs. b: OR = 0.865, 95% CI: 0.760–0.983, p= 0.026; AA vs. aa: OR = 1.329, 95% CI: 1.016–1.740, p= 0.038). The VDR BsmI and FokI polymorphisms were correlated with SLE in African subjects (B vs. b: OR = 1.898, 95% CI: 1.458–2.470, p＜0.01; BB + Bb vs. bb: OR = 2.935, 95% CI: 1.944–4.430, p< 0.01; FF vs. Ff + ff: OR = 2.424, 95% CI: 1.673–3.512, p< 0.01; F vs. f: OR = 1.720, 95% CI: 1.417–2.087, p< 0.01; FF vs. ff: OR = 3.154, 95% CI: 2.083–4.774, p< 0.01; FF + Ff vs. ff: OR = 1.803, 95% CI: 1.363–2.384, p< 0.01). In addition, the VDR Apal polymorphism was correlated with SLE in female subjects (AA vs. aa: OR = 1.392, 95% CI: 1.049–1.849, p= 0.022) when stratified by gender. But there was no association between the VDR TaqI polymorphism and SLE susceptibility in our analysis.Conclusions:The VDR Apal polymorphism was associated with SLE susceptibility in general populations; in addition, Apal polymorphism was associated with SLE in female subjects. The VDR Bsml gene polymorphism was correlated with SLE susceptibility in Caucasian and African populations, whereas the VDR FokI polymorphism was correlated with SLE in African populations. But there was no association between the VDR TaqI polymorphism and SLE susceptibility in our analysis.

Group 2 innate lymphoid cells (ILC2s) play an important role in allergic airway inflammation. Despite recent advances in defining molecular mechanisms that control ILC2 development and function, the role of endogenous metabolites in the regulation of ILC2s remains poorly understood. Herein, we demonstrated that bilirubin, an end product of heme catabolism, was a potent negative regulator of ILC2s. Bilirubin metabolism was found to be significantly induced during airway inflammation in mouse models. The administration of unconjugated bilirubin (UCB) dramatically suppressed ILC2 responses to interleukin (IL)−33 in mice, including cell proliferation and the production of effector cytokines. Furthermore, UCB significantly alleviated ILC2-driven airway inflammation, which was aggravated upon clearance of endogenous UCB. Mechanistic studies showed that the effects of bilirubin on ILC2s were associated with downregulation of ERK phosphorylation and GATA3 expression. Clinically, newborns with hyperbilirubinemia displayed significantly lower levels of ILC2 with impaired function and suppressed ERK signaling. Together, these findings indicate that bilirubin serves as an endogenous suppressor of ILC2s and might have potential therapeutic value in the treatment of allergic airway inflammation.

We used a diamond anvil cell(DAC) to control the deformation of synthesized copper nanorods and silver nanoparticles. And we measured the surface plasmon resonance of copper nanorods and silver nanoparticles, which exhibit redshifts or blueshifts. The surface plasmon resonance shows an abnormal blue shift for both copper nanorods and silver nanoparticles. The solvents of copper nanorods and silver nanoparticles are n-hexane and water, where the pressure loads include quasi-hydrostatic and non-hydrostatic.

This work explored the microstructure, mechanical properties, and the related fracture mechanism of electron beam welded (EBW) IN738LC joints subjected to partial post-weld heat treatment (P-PWHT) and full post-weld heat treatment (F-PWHT). The two PWHT schedules produced a significant effect on the microstructure and mechanical properties of IN738LC joints. The fusion zone (FZ) presented a similar microstructure with BM, composed of duplex-sized γ′ particles, blocky MC carbides, and continuous M23C6 carbides. While F-PWHT resulted in the complete dissolution of primary γ′ particles and unimodal-spheroidal γ′ particles were obtained in IN738LC joint. The size and amount of γ′ particles in FZand BM of the joints after F-PWHT were higher than that of IN738LC joints subjected to P-PWHT. In addition, F-PWHT also facilitated the dissolution of MC carbides, releasing more free C atoms. High amount of M23C6 carbides consequentially formed along grain boundaries (GBs) in IN738LC joints. Compared with F-PWHT, the formation of duplex-sized γ′ particles and less M23C6 carbides in FZand BM weakened the tensile strength (900 °C) but improved the elongation (16.6%) of P-PWHTed joints. The retained primary γ′ particles and minor M23C6 carbides in FZof IN738LC joints after P-PWHT retarded the GB sliding, bringing about a higher stress-rupture life, about 2.5 h (900 °C/350 MPa).

Understanding the spatial structure of genetic diversity provides insights into a populations’ genetic status and enables assessment of its capacity to counteract the effects of genetic drift. Such knowledge is particularly scarce for the snow leopard, a conservation flagship species of Central Asia mountains. Focusing on a snow leopard population in the Qilian mountains of Gansu Province, China, we characterised the spatial genetic patterns by incorporating spatially explicit indices of diversity and multivariate analyses, based on different inertia levels of Principal Component Analysis (PCA). We compared two datasets differing in the number of loci and individuals. We found that genetic patterns were significantly spatially structured and were characterised by a broad geographical division coupled with a fine-scale cline of differentiation. Genetic admixture was detected in two adjoining core areas characterised by higher effective population size and allelic diversity, compared to peripheral localities. The power to detect significant spatial relationships depended primarily on the number of loci, and secondarily on the number of PCA axes. Spatial patterns and indices of diversity highlighted the cryptic structure of snow leopard genetic diversity, likely driven by its ability to disperse over large distances. In combination, the species’ low allelic richness and large dispersal ability result in weak genetic differentiation related to major geographical features and isolation by distance. This study illustrates how cryptic genetic patterns can be investigated and analysed at a fine spatial scale, providing insights into the spatially variable isolation effects of both geographic distance and landscape resistance.

A novel α+β titanium alloy with multi-alloying addition was designed based on the cluster formula 12[Al-Ti12](AlTi2)+5[Al-Ti14](AlV12Mo06Nb02) which was derived from Ti-6Al-4V. The nominal composition of this novel alloy was determined as Ti-6.83Al-2.28V-2.14Mo-0.69Nb-6.79Zr. In this study, the novel alloy and Ti-6Al-4V alloy samples were prepared by laser additive manufacturing. The microstructure, micro-hardness, room/high temperature tensile properties of the as-deposited samples were investigated. Compared to Ti-6Al-4V, the novel alloy has much higher room and high temperature (600 °C) tensile strengths, which are 1,427.5 MPa and 642.2 MPa, respectively; however, it has a much lower elongation (3.2%) at room temperature because of the finer microstructure. To improve the elongation of the novel alloy, heat treatment was used. After solution at 960 °C or 970 °C for 1 h followed by air cooling and aging at 550 °C for 4 h followed by air cooling, a unique bi-modal microstructure which contains crab-like primary α and residual β phase is obtained, improving the compression elongation by 80.9% compared to the as-deposited samples. The novel alloy can be used as a high-temperature and high-strength candidate for laser additive manufacturing.

Gastric cancer (GC) is one of the most common digestive system tumors in the world. Many circular RNAs (circRNAs) are involved in the progression of GC. The purpose of this study was to delve into the expression characteristics and biological functions of circ_0000064 in GC, and further study its mechanisms. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to detect circ_0000064 expression in 61 GC tissues and cell lines. Circ_0000064 knockdown was successfully modeled with siRNA. The effects of circ_0000064 on the biological functions of GC cells were analyzed by CCK‐8, BrdU, and Transwell assays. Bioinformatics and dual‐luciferase reporter gene assay were adopted to explore the relations between circ_0000064 and microRNA‐621 (miR‐621). Western blot was used to examine the regulatory function of circ_0000064 and miR‐621 on SYF2 pre‐mRNA splicing factor 2. Cric_0000064 expression was elevated in GC tissues and cell lines. Knocking down cric_0000064 could inhibit the viability, migration, and invasion of GC cells. Dual‐luciferase reporter gene assay showed that miR‐621 could bind circ_0000064 and SYF2 3'UTR; in addition, miR‐621 overexpression or SYF2 knockdown could partially weaken the cancer‐promoting effect of circ_0000064 on GC cells. Circ_0000064 expression was negatively correlated with miR‐621 expression in GC tissues while positively with SYF2 expression. Circ_0000064 can participate in the GC progression via modulating miR‐621/SYF2 axis. This implies that circ_0000064 may be a new diagnosed biomarker or a new therapeutic target of GC.

The drying shrinkage of geopolymers poses significant limitations on their potential as constructive materials. In this study, the drying shrinkage of metakaolin-based geopolymer (MKG) with different initial water/solid ratios and pore structures was investigated experimentally. According to mini-bar shrinkage experiments, the drying shrinkage-water loss relation of MKG showed two-stage behavior. The initial water/solid ratio influences the critical water loss and span of the pausing period of the shrinkage curves but not the general trend. Combined with the microstructure characterization and physical estimation, the underlying dependency of the shrinkage on the pore structure of the binder was elucidated. Capillary pressure, surface energy change, and gel densification dominate the drying shrinkage of MKG at different water loss stages. The findings indicate that besides porosity control, finer tuning of the pore size distribution is needed to control the drying shrinkage of MKG.

With the rapid development of information technology, information security has been gaining attention. The International Organization for Standardization (ISO) has issued international standards and technical reports related to information security, which are gradually being adopted by enterprises. This study analyzes the relationship between information security certification (ISO 27001) and corporate financial performance using data from Chinese publicly listed companies. The study focusses on the impact of corporate decisions such as whether to obtain certification, how long to hold certification, and whether to publicize information regarding certification. The results show that there is a positive correlation between ISO 27001 and financial performance. Moreover, the positive impact of ISO 27001 on financial performance gradually increases with time. In addition, choosing not to publicize ISO 27001 certification can negatively affect enterprise performance.

Kidney disease is a serious health problem that burdens our healthcare system. It is crucial to find the accurate pathogenesis of various types of kidney disease to provide guidance for precise therapies for patients suffering from these diseases. However, the exact molecular mechanisms underlying these diseases have not been fully understood. Disturbance of calcium homeostasis in renal cells plays a fundamental role in the development of various types of kidney disease, such as primary glomerular disease, diabetic nephropathy, acute kidney injury and polycystic kidney disease, through promoting cell proliferation, stimulating extracellular matrix accumulation, aggravating podocyte injury, disrupting cellular energetics as well as dysregulating cell survival and death dynamics. As a result, preventing the disturbance of calcium homeostasis in specific renal cells (such as tubular cells, podocytes and mesangial cells) is becoming one of the most promising therapeutic strategies in the treatment of kidney disease. The endoplasmic reticulum and mitochondria are two vital organelles in this process. Calcium ions cycle between the endoplasmic reticulum and mitochondria at the conjugation of these two organelles known as the mitochondria-associated endoplasmic reticulum membrane, maintaining calcium homeostasis. The pharmacologic modulation of cellular calcium homeostasis can be viewed as a novel therapeutic method for renal diseases. Here, we will introduce calcium homeostasis under physiological conditions and the disturbance of calcium homeostasis in kidney diseases. We will focus on the calcium homeostasis regulation in renal cells (including tubular cells, podocytes and mesangial cells), especially in the mitochondria- associated endoplasmic reticulum membranes of these renal cells.

Diabetes Wound Dressing In article 2303042, Zhiyong Qian and co‐workers report a multifunctional hydrogel wound dressing for diabetic wounds infected with bacteria. This hydrogel dressing exhibit excellent antibacterial properties, adhesion, and mild stimulation‐triggered detachment, offering a potential avenue for the development of painless antibacterial dressings.

In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the double-improved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function.

This study explores the impact of Occupational Health and Safety Assessment Series 18001 (OHSAS 18001) certification on innovation efficiency in green management and seeks to assist senior managers in understanding the ideal structural environment to maximise the innovation potential of the certification system. We examine the ownership status of organisations and the pay disparity between employees and executives to determine whether they influence the ability of OHSAS 18001 to promote innovation efficiency. We analyse data from 1,905 Chinese listed companies using stochastic frontier analysis to determine the innovation efficiency of OHSAS 18001-certified companies. We find that OHSAS 18001 stimulates firm innovation efficiency. However, this improvement in innovation efficiency is dependent on the level of pay disparity between executive and non-executive employees. We also demonstrate that the effect of OHSAS 18001 on innovation efficiency is closely related to enterprise ownership, whereby state-owned enterprises are less likely to realise the innovation potential of OHSAS 18001 than privately-owned organisations are.

Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others.

The search for cost-effective and highly active transition-metal-based electrocatalysts is of great importance for overall water splitting to generate clean energy hydrogen. In this work, we present a controllable structural transformation engineering strategy to construct 3D hierarchical CoP porous microscale prism-like superstructure (assembled with nanoflakes) arrays grown on surface-phosphatized Ni foam (CoP/SPNF). Specifically, Zn/Co-based composite arrays with a nanowires@prism hierarchical structure were prepared on Ni foam first. Then, porous Co-based compound arrays with a nanoflakes@prism hierarchical structure were obtained through removing the Zn-based compound by alkaline etching. Finally, CoP arrays were produced through phosphatization of the prepared Co-based array precursor, using NaH2PO2·H2O as the P source. The fabricated CoP/SPNF electrocatalyst exhibits impressive bifunctional performance for the hydrogen evolution reaction (HER, overpotential of 45 mV at 10 mA cm–2) and oxygen evolution reaction (OER, overpotential of 215 mV at 80 mA cm–2) and consequently enables efficient electrolytic water splitting with a low cell voltage of 1.547 V at 30 mA cm–2and a prominent durability. Versatile CoP with its porous superstructure arrays on surface-phosphatized Ni foam can increase the exposure of electrochemically active sites and render easy contact with the electrolyte, thus facilitating fast electron transport and effective electrolyte diffusion during the electrocatalytic process, as well as promoting the release of product gas bubbles from the electrode. This work provides an effective strategy for the design and preparation of non-noble-metal bifunctional electrocatalysts for overall water splitting electrolysis.

An enantioselective cyclization of diazoindolinones with o-hydroxymethyl chalcones has been established by a cooperative dirhodium complex and chiral phosphonic acid catalysis under mild conditions. This reaction is the first example of catalytic asymmetric intramolecular Michael-type trapping of oxonium ylide enabled by phosphoric acid through a dual H-bonding activation model, which provides an efficient access to the chiral spirochroman-3,3-oxindoles, with vicinal quaternary and tertiary stereocenters, in good to excellent yields and enantioselectivities.