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Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection. Effective treatment of bacterial sepsis remains a paramount clinical challenge, due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. Here, we present a decoy nanozyme-enabled intervention strategy for multitarget blockade of proinflammatory cascades to treat multi-drug-resistant (MDR) bacterial sepsis. The decoy nanozymes (named MCeC@MΦ) consist mesoporous silica nanoparticle cores loaded with CeO2 nanocatalyst and Ce6 photosensitizer and biomimetic shells of macrophage membrane. By acting as macrophage decoys, MCeC@MΦ allow targeted photodynamic eradication of MDR bacteria and realize simultaneous endotoxin/proinflammatory cytokine neutralization. Meanwhile, MCeC@MΦ possess intriguing superoxide dismutase and catalase-like activities as well as hydroxyl radical antioxidant capacity and enable catalytic scavenging of multiple reactive oxygen species (ROS). These unique capabilities make MCeC@MΦ to collaboratively address the issues of bacterial infection, endotoxin/proinflammatory cytokine secretion, and ROS burst, fully cutting off the path of proinflammatory cascades to reverse the progression of bacterial sepsis. In vivo experiments demonstrate that MCeC@MΦ considerably attenuate systemic hyperinflammation and rapidly rescue organ damage within 1 day to confer higher survival rates (>75%) to mice with progressive MDR Escherichia coli bacteremia. The proposed decoy nanozyme-enabled multitarget collaborative intervention strategy offers a powerful modality for bacterial sepsis management and opens up possibilities for the treatment of cytokine storm in the COVID-19 pandemic and immune-mediated inflammation diseases.

Ground military target recognition plays a crucial role in unmanned equipment and grasping the battlefield dynamics for military applications, but is disturbed by low-resolution and noisyrepresentation. In this paper, a recognition method, involving a novel visual attention mechanismbased Gabor region proposal sub-network (Gabor RPN) and improved refinement generative adversarial sub-network (GAN), is proposed. Novel centraleperipheral rivalry 3D color Gabor filters are proposed to simulate retinal structures and taken as feature extraction convolutional kernels in low-level layer to improve the recognition accuracy and framework training efficiency in Gabor RPN. Improved refinement GAN is used to solve the problem of blurry target classification, involving a generator to directly generate large high-resolution images from small blurry ones and a discriminator to distinguish not only real images vs. fake images but also the class of targets. A special recognition dataset for ground military target, named Ground Military Target Dataset (GMTD), is constructed. Experiments performed on the GMTD dataset effectively demonstrate that our method can achieve better energy-saving and recognition results when low-resolution and noisy-representation targets are involved, thus ensuring this algorithm a good engineering application prospect. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report. [ABSTRACT FROM AUTHOR]

Asperger syndrome (AS) is a chronic neurodevelopmental disorder. Although all of the clinically diagnosed cases display normal intelligence and speech functions, barriers in social interaction and communication seriously affect mental health and psychological function. In addition to traditional psychological/behavioral training and symptomatic medication, in-depth studies of intestinal microbiota and mental health have indicated that probiotics (e.g., Lactobacillus rhamnosus) can effectively reduce the occurrence of AS. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient’s gastrointestinal tract to improve the gut microenvironment. In this case report, we describe the first case of adult AS treated with FMT. The patient suffered from diarrhea-predominant irritable bowel syndrome for 6 years with symptoms of diarrhea and abdominal pain. After three rounds of FMT, the diarrhea and abdominal pain were significantly improved. Moreover, the symptoms of AS were also significantly ameliorated. We found that FMT changed the structure of the intestinal microbiota as well as the patient’s serum metabolites, and these changes were consistent with the patient’s symptoms. The metabolites may affect signaling pathways, as revealed by Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The changes in microbial metabolites following FMT may affect other regions (e.g., the nervous system) via the circulatory system, such that the bacteria-gut-blood-brain axis may be the means through which FMT mitigates AS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Carboxylesterase (CarE) is a major class of enzyme involved in the detoxification of toxic xenobiotics in various insect species. Previous work has shown that the carboxylesterase gene CarE001G found in Helicoverpa armigera is more active and can metabolize synthesized pyrethroids, such as β-cypermethrin, one of the commonly used commercial insecticides for lepidopteran pest control. In addition, CarE001G is very special as it has a very specific glycine-rich region located adjacent to its C-terminal. But whether mutations in this unique sequence can change the biochemistry and function of CarE001G are unknown. RESULTS: In this study, four variants of CarE001G with different deletions in the glycine-rich region were obtained and functionally expressed in Escherichia coli. The recombinant proteins were purified and confirmed by Western blot and mass spectrometry analyses. These mutant enzymes showed high catalytic efficiency toward the model substrate α-naphthyl acetate. Inhibition study showed that β-cypermethrin had relatively strong inhibition on CarE activities. In vitro metabolism assay showed that the mutant enzymes significantly enhanced their metabolic activities toward β-cypermethrin with specific activities between 4.0 and 5.6 nmol L-1 min−1 mg−1 protein. Molecular docking analyses consistently demonstrated that deletion mutations in the glycine-rich region may facilitate the anchoring of the β-cypermethrin molecule in the active binding pocket of the mutant enzymes. CONCLUSION: The data show that deletion mutations can cause qualitative change in the capacity of CarEs in the detoxification of β-cypermethrin. This indicates that deletion mutations in the glycine-rich region may have the potential to cause synthesized pyrethroid (SP) resistance in H. armigera in the future. [ABSTRACT FROM AUTHOR]

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic Escherichia coli (EPEC) by shutting down an infection-responsive signal of the host intestine cell. A key step in EPEC infection of intestinal cells involves Tir-induced actin reorganization. Nck mediates this event by binding with Tir through its SH2 domain (Nck-SH2) and with WIP through its second SH3 domain (Nck-SH3.2). Here we report the design of a synthetic peptide that reacts precisely with a unique cysteine of the Nck-SH3.2 domain, blocks the binding site of the Nck protein, and prevents EPEC infection of Caco-2 cells. Oral update of this nontoxic peptide before EPEC administration safeguards mice from EPEC infection and diarrhea. This study demonstrates domain-specific blockage of an SH3 domain of a multidomain adaptor protein inside cells and the inhibition of Tir-induced rearrangement of the host actin cytoskeleton as a previously unknown antibacterial mechanism. [ABSTRACT FROM AUTHOR]

In China, the desulfurization problem of power plants has been paid much attention by the government and the public. From 2014 to present, the nearly one hundred million tons of desulfurized gypsum has been discharged. The utilization rate of desulfurized gypsum in power plants has also become the focus of current research. The purpose of this study is to study the influence of aluminum powder and NaOH on the physical and mechanical properties of desulfurized gypsum aerated block(DGAB). The testing results show that when the optimized formula is 5% high-alumina cement, 0.7% aluminum powder, 0.5% NaOH, 0.6 water-cement ratio and the producing gas temperature is 40°C, the physical and mechanical properties of DGAB can reach the bulk density of 309.3 kg/m3, the strength of 0.24 MPa, and the thermal conductivity of 0.073 W/(m·K). The microscopic analysis showed that when the amount of aluminum powder was 0.7%, the porosity of DGAB was minimum, its pore size was uniform and smaller than 1 mm, and the insulation effect was better. At this time, the strength of DGAB can reach the highest value and the thermal conductivity of DGAB is lower. [ABSTRACT FROM AUTHOR]

Saline soils, which are mainly found in the arid/semi-arid climatic areas and coastal regions, are widespread all of the world, having limited potential for cultivation. This paper presents a study explored an alternative way by using alkali activated saline soil combined with fly ash to form geopolymer to develop the building materials with ultra-low embodied energy and CO2 for sustainable construction. The properties of the alkali-activated geopolymer made with saline soil-fly ash combination were evaluated. With the study on the effects of the mix proportions and process technics, the production of the geopolymer was optimised. The study indicates that the ideal conditions for the dissolution of SiO2 and Al2O3 were 10M NaOH at 60°C for 24 hours. The saline soil-fly ash combination has good physical and mechanical properties and durability, which were increased with the fly ash content from 20% to 60%. XRD, FTIR and SEM were applied to analyse the reaction mechanism and microstructures of the alkali-activated saline soil-fly ash system. After alkali-activation, depolymerisation and reconstruction of the activated silicate and aluminate formed zeolite-liked gel products and generated aluminium silicate network structures, which is the key for the performance of the material obtained. The microstructure of product varied with the fly ash content in the system, affecting the density of the products. [ABSTRACT FROM AUTHOR]

The paper adopted a bionic hemispherical convex structure in the A pillar-rear view mirror regions according to actual requirements. Furthermore, impacts of the bionic structure on aerodynamic characteristics and noises in the region were studied. Friction resistance of airflows was greatly reduced, fluctuations and pulsation pressures of flow fields were also reduced, and characteristics of flow fields and sound fields were improved. The computational results were finally verified by the experimental test. Firstly, the aerodynamic lift force coefficient and drag force coefficient of the bionic model were computed, and they were obviously lower than those of the original model. The adhesive force between tires and ground during vehicle running was increased, and the danger degree of "waving" of high-speed vehicle running was weakened. In this way, stability of vehicle running could be improved. Secondly, flow fields of the bionic model were computed. Compared with the original model, an obvious vortex was behind the original model, while no vortexes were behind the bionic model. Therefore, convex structures of the bionic model had obvious impacts on flow fields behind the rear view mirror. Airflow separation situations were obvious improved at wheels, windshield and rear side windows of the bionic model. Due to blocking of convex structures of the A pillar and rear view mirror in the bionic model, airflows was hindered and obvious dragging phenomena were formed. Therefore, flow fields in the side window regions could be improved greatly. In addition, the flow field scope under the rear view mirror in the bionic model was also decreased. Ringed vortex structures appeared behind the rear view mirror in the bionic model. The ringed vortex structures were closely interlaced and then extended together backwards. Vortexes behind the rear view mirror in the original model were chaotic, where most of them were attached on the surface of side windows. In the original model, turbulent flows with certain strength were on the right upper corner of the side window region. In the bionic model, no turbulent flows were in the same regions. This result indicated that through using the bionic convex structures, airflows flowing through side windows could be combed and could move backwards towards upper and lower edges of the side windows. It could be predicted that pulsation pressures on the side window surface would surely decrease. Therefore, aerodynamic noises caused by pulsation pressures in side window regions would also be improved correspondingly. Especially in regions behind A pillar-rear view mirrors, the maximum noise reduction amplitude reached about 20 dB. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the ultrastructural damage and the expression of heat shock protein 70 (HSP70) in the rat adenohypophysis following pulsed electromagnetic wave (PEMW) exposure. The rats were randomly divided intofour groups: Sham PEMW exposure, 1x104 pulses of PEMW exposure, 1x105 pulses of PEMW exposure and 3x105 pulses of PEMW exposure. Whole body radiation of 1x104 pulses, 1x105 pulses and 3x105 pulses of PEMW were delivered with a field strength of 100 kV/m. The rats in each group (n=6 in each) were sacrificed 12, 24, 48 and 96 h after PEMW exposure. Transmission electron microscopy was then used to detect the ultrastructural changes and immunocytochemistry was used to examine the expression of HSP70. Cellular damage, including mitochondrial vacuolation occurred as early as 12 h after PEMW exposure. More severe cellular damages, including cell degeneration and necrosis, occurred 24 and 48 h after PEMW exposure. The PEMW-induced cellular damage increased as the number of PEMW pulses increased. In addition, the expression of HSP70 significantly increased following PEMW exposure and peaked after 12 h. These findings suggested that PEMW induced ultrastructural damages in the rat adenohypophysis and that HSP70 may have contributed to the PEMW-induced adenohypophyseal damage. [ABSTRACT FROM AUTHOR]

Background Galectin-3, a member of the beta-galactoside-binding lectin family, is a multifunctional protein with various biological functions, including the proliferation and differentiation of tumor cells, angiogenesis, cancer progression, and metastasis. We aimed to clarify if expression of galectin-3 is related to the clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC) patients, and to explore the possible mechanisms of galectin-3 in hepatocellular carcinoma. Methods First, we investigated galectin-3 mRNA and protein expression by using RT-PCR and Western blotting. Second, tissues from 165 HCC patients were used to evaluate clinicopathological characteristics and prognosis through immunohistochemical analyses. Furthermore, the functions of galectin-3 were analyzed with respect to the proliferation, cell cycle,apoptosis, migration, and invasion of HCC cell lines. Finally, we analyzed galectin-3 expression and micro-vessel density (MVD) by immunohistochemistry (IHC) to find its correlation with angiogenesis in Hepatocellular Carcinoma. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. Results Galectin-3 showed high expression at the mRNA and protein levels in HCC cancer tissues and cell lines. Clinicopathological analyses revealed that increased expression of galectin-3 in tumors was closely associated with a poor prognosis. Galectin-3 knockdown by siRNA significantly inhibited cell growth, migration, and invasion, and induced apoptosis in HCC cells in vitro, whereas galectin-3 overexpression promoted cell growth, migration, and invasion. Correlation analysis of galectin-3 expression and micro-vessel density (MVD) showed that galectin-3 expression in tumor cells stimulates angiogenesis. The observed regulation of cell apoptosis was accompanied by the galectin-3-mediated modulation of caspase3 signaling pathways in HCC cells. Conclusions These data suggest that galectin-3 plays an important part in HCC progression and may serve as a prognostic factor for HCC. [ABSTRACT FROM AUTHOR]

Background: The ARID1A gene encodes adenine-thymine (AT)-rich interactive domain-containing protein 1A, which participates in chromatin remodeling. ARID1A has been showed to function as a tumor suppressor in various cancer types. In the current study, we investigated the expression and prognosis value of ARID1A in primary gastric cancer. Meanwhile, the biological role of ARID1A was further investigated using cell model in vitro. Methodology/Principal Findings: To investigate the role of ARID1A gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were used to examine the ARID1A expression in paired cancerous and noncancerous tissues. Results revealed decreased ARID1A mRNA (P = 0.0029) and protein (P = 0.0015) expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues, and in gastric cancer cell lines. To further investigate the clinicopathological and prognostic roles of ARID1A expression, we performed immunohistochemical analyses of the 224 paraffin-embedded gastric cancer tissue blocks. Data revealed that the loss of ARID1A expression was significantly correlated with T stage (P = 0.001) and grade (P = 0.006). Consistent with these results, we found that loss of ARID1A expression was significantly correlated with poor survival in gastric cancer patients (P = 0.003). Cox regression analyses showed that ARID1A expression was an independent predictor of overall survival (P = 0.029). Furthermore, the functions of ARID1A in the proliferation and colony formation of gastric cell lines were analyzed by transfecting cells with full-length ARID1A expression vector or siRNA targeting ARID1A. Restoring ARID1A expression in gastric cancer cells significantly inhibited cell proliferation and colony formation. Silencing ARID1A expression in gastric epithelial cell line significantly enhanced cell growth rate. Conclusions/Significance: Our data suggest that ARID1A may play an important role in gastric cancer and may serve as a valuable prognostic marker and potential target for gene therapy in the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the expression and prognostic significance of activator protein 2&agr; (AP-2&agr;) in gastric adenocarcinoma. Methodology/Principal Findings: AP-2&agr; expression was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining methods on tissue samples from a consecutive series of 481 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between AP-2&agr; expression, clinicopathological factors, and patient survival was investigated. RT- qPCR results showed that the expression of AP-2&agr; mRNA was reduced in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples (P = 0.009); this finding was confirmed by western blotting analysis (P = 0.012). Immunohistochemical staining data indicated that AP-2&agr; expression was significantly decreased in 196 of 481 (40.7%) gastric adenocarcinoma cases; reduced AP-2&agr; expression was also observed in patients with poorly differentiated tumors (P = 0.001) and total gastric carcinomas (P = 0.002), as well as in patients who underwent palliative tumor resection (P = 0.004). Additionally, reduced expression of AP-2&agr; was more commonly observed in tumors that were staged as T4a/b (P = 0.018), N3 (P = 0.006), and M1 (P = 0.008). Kaplan-Meier survival curves revealed that reduced expression of AP-2&agr; was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified AP-2&agr; expression as an independent prognostic factor for overall survival (HR = 1.512, 95% CI = 1.127-2.029, P = 0.006). Conclusions/Significance: Our data suggest that AP-2&agr; plays an important role in tumor progression and that reduced AP- 2&agr; expression independently predicts an unfavorable prognosis in gastric adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

Here the distance dependence of metal-enhanced quantum dots (QDs) fluorescence in solution is studied systematically by capillary electrophoresis (CE). Complementary DNA oligonucleotides-modified CdSe/ZnS QDs and gold nanoparticles (Au NPs) were connected together in solution by the hybridization of complementary oligonucleotides, and a model system (QD-Au) for the study of metal-enhanced QDs fluorescence was constructed, in which the distance between the QDs and Au NPs was controlled by adjusting the base number of the oligonucleotide. In our CE experiments, the metal-enhanced fluorescence of the QDs solution was only observed when the distance between the QDs and Au NPs ranged from 6.8 to 18.7 nm, and the maximum enhancement by a factor of 2.3 was achieved at 11.9 nm. Furthermore, a minimum of 19.6 pg of target DNA was identified in CE based on its specific competition with the QD-DNA in the QD-Au system. This work provides an important reference for future study of metal-enhanced QDs fluorescence in solution and exhibits potential capability in nucleic acid hybridization analysis and high-sensitivity DNA detection. [ABSTRACT FROM AUTHOR]

In this article, water-soluble CdTe/CdS quantum dots (QDs) were synthesized in aqueous solution with captosuccinic acid as stabilizer. The absorption and fluorescence spectra showed that the as-prepared QDs had good optical properties. It was observed that the quantum yield (QY) of QDs was greatly increased after a heating–cooling cycle (from 22 to 41%). Then, the QDs were used to prepare fluorescent probes. The experiment results showed that the transferrin (Tf) could conjugate to QDs effectively and the HepG2 cells could be recognized successfully. This study is of great significance for the preparation of high-quality QDs and their applications in life science. [ABSTRACT FROM AUTHOR]

A duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was improved for simultaneous detection of highly pathogenic H5N1 avian influenza virus and pandemic H1N1 (2009) influenza virus, which is suitable for early diagnosis of influenza-like patients and for epidemiological surveillance. The sensitivity of this duplex real-time RT-PCR assay was 0.02 TCID50 (50% tissue culture infective dose) for H5N1 and 0.2 TCID50 for the pandemic H1N1, which was the same as that of each single-target RT-PCR for pandemic H1N1 and even more sensitive for H5N1 with the same primers and probes. No cross reactivity of detecting other subtype influenza viruses or respiratory tract viruses was observed. Two hundred and thirty-six clinical specimens were tested by comparing with single real-time RT-PCR and result from the duplex assay was 100% consistent with the results of single real-time RT-PCR and sequence analysis. [ABSTRACT FROM AUTHOR]

Single administration of low dose cyclophosphamide (CTX) was previously reported to enhance the antitumor efficacy of immunotherapies. To investigate the possible mechanisms for this effect, we examined whether a single administration of low dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty milligrams per kilogram body weight dose of CTX was administrated intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models were established, DC vaccine generated from mouse bone marrow and pulsed with B16 or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment potentiated the antitumor effects of the DC vaccine, and increased the proportion of IFN-γ secreting lymphocytes in spleens. Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX. Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Treg cells in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced immunopotentiation and provided a strategy of immunotherapy combining a low dose CTX with DC vaccine. [ABSTRACT FROM AUTHOR]

The present study is, to the best of our knowledge, the first report of a rare, transient form of unilateral facial paralysis induced by perimesencephalic non-aneurysmal subarachnoid hemorrhage. The paralysis may have resulted from the compression of a part of the facial nerve by the low of the hemorrhage into the cavum subarachnoidale; alternatively, the paralysis may have been caused by disorder of the blood supply of the facial nucleus, with the hemorrhage leading to brainstem vasospasm. The patient underwent hemostatic therapy, administration of a symptomatic antiemetic and dehydration. The facial nerve compression was released due to the absorption of the hemorrhage or the rapid improvement of the facial nucleus blood supply following the resolution of the vasospasm. Consequently, the facial nerve function was fully recovered, and the facial paralysis disappeared. [ABSTRACT FROM AUTHOR]

Groundwater-Dependent Ecosystems (GDEs) in the arid region of northwest China are crucial for maintaining ecological balance and biodiversity. However, the ongoing decline in groundwater levels caused by excessive groundwater exploitation poses a potential threat to GDEs. This paper reviews the current developments and future challenges associated with defining groundwater level thresholds for maintaining GDEs in arid regions. It focuses on methods for identifying and investigating these thresholds, with particular attention to recent advances in northwest China. Additionally, this paper highlights the limitations and future challenges in determining these thresholds, including the complexities of ecological processes, groundwater systems, data availability, and methodological constraints. To address these issues, a multidisciplinary approach that incorporates new technologies, such as multi-source data fusion, machine learning models, and big data and cloud computing, will be essential. By overcoming these challenges and utilizing effective methods, appropriate groundwater level thresholds can be established to ensure the long-term sustainability of GDEs.

Purpose: ensure increase of effectiveness of training process’s control by means of operative correction of training loads of different qualification judo wrestlers’ heart beats rate indicators. Material: the research was conducted on the base of Brest SCJSOR № 1. Judo wrestlers of different sport qualification (age 17-19 years old, n=15) participated in the research. Monitoring of judo wrestlers’ heart beats rate was carried out with the help of system “Polar”. Results: we have found factorial structure of functional fitness in every profile of sportsmen. Model characteristics of judo wrestlers were supplemented with the most important sides of functional fitness. Analysis of indicators of restoration effectiveness indicators (REI) in both groups of judo wrestlers showed high level of organism’s responsiveness to training load of special and power orientation in comparison with speed power load. We have worked out algorithm of operative correction of training loads by indicators of heart beats rate in training process, depending on orientation and intensity of loads’ physiological influence on judo wrestler. Conclusions: Telemetric on-line monitoring of sportsman’s heart beats rate and calculation of REI permit to objectively assess effectiveness of training’s construction and of micro-cycle in total and detect in due time the trend to development of over-loading and failure of adaptation.

Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries. In this study, we designed, synthesized, and characterized novel Ejiao carbon dots (EJCDs) that inhibit myeloid cell proliferation and peripheral migration by promoting HSC self-renewal, and distinct differentiation into erythroid progenitors in vitro and in vivo. Additionally, EJCDs attenuate the immune response in the spleen, leukocytes’ reservoir, following spinal cord injury by diminishing the local infiltration of monocytes and macrophages while promoting motor function recovery. These effects are mediated through the downregulation of CCAAT enhancer binding protein-β expression in the spleen and the upregulation of FZD4 protein expression in Lin− Sca-1+ c-kit+ cells (LSKs) within the bone marrow. Our findings demonstrate that EJCDs effectively reduce myeloid cell infiltration post-spinal cord injury and promote neurological recovery, making them promising therapeutic candidates for treating spinal cord injuries.

Purpose: experimental substantiation of methodic of junior boxers’ coordination training. Material: in the research 18 boxers of 11-13 year old age participated. In total, during 4 months 42 trainings were conducted. Total time of coordination load’s fulfillment at each training was 15-45 minutes. Results: dynamic of results in control tests was statistically confident in the tested parameters of movements. It proves effectiveness of usage the tasks with complex-coordination orientation, accented on impact on sensor-informational and motor systems of movements in junior boxers’ trainings. Conclusions: coordination training in boxing at initial stage shall include specialized varied means and methods, which would facilitate formation of motor condition and skills’ basis. Motor condition and skills are a reserve for further rising of coordination abilities’ level of junior sportsmen.

Purpose: to identify interferences psychomotor abilities for consistency in the management of spatio-temporal parameters of procedural and final precision in the movements with complex motor structure. Material : the study involved 30 people occupying the eastern species physical culture (Wushu Qigong and Tai Chi Chuan). Results : It was found that the identified trusted connection as positive (n = 59, r = 0.63 to 0.92) and negative (n = 21, r = from -0.63 to -0.89) confirm the influence of particular classes in the eastern system ability to coordinated control movements of different coordination complexity. Conclusions : the ability to control the internal forces, the ability to focus, alertness and mind control depend on three complementary levels - substance "Jing", "Qi" and "Shen", which directly affect the state of psychomotor sphere and target accuracy of spatio-temporal motion parameters.

The optical properties of antiphotobleaching and the advantage of long-term fluorescence observation of quantum dots are fully adopted to study the effects of iron on the endocytosis of transferrin. Quantum dots are labeled for transferrin and endocytosis of transferrin in HeLa cells is observed under the normal state, iron overloading, and an iron-deficient state. In these three states, the fluorescence undergoes a gradual process of first dark, then light, and finally dark, indicating the endocytosis of transferrin. The fluorescence intensity analysis shows that a platform emerges when fluorescence changes to a certain degree in the three states. Experienced a same period of time after platform, the fluorescence strength of cells in the normal state is 1.2 times the first value, and the iron-deficiency state is 1.4 times, but the iron overloading state was 0.85 times. We also find that the average fluorescence intensity in cells detected by the spectrophotometer in the iron-deficiency state is almost 7 times than that in a high iron state. All this proves that iron overloading would slow the process, but iron deficiency would accelerate endocytosis. We advance a direct observational method that may contribute to further study of the relationship of iron and transferrin. [ABSTRACT FROM AUTHOR]

Abstract The management of diabetic ulcer (DU) to rescue stalled wound healing remains a paramount clinical challenge due to the spatially and temporally coupled pathological wound microenvironment that features hyperglycemia, biofilm infection, hypoxia and excessive oxidative stress. Here we present a pH-switchable nanozyme cascade catalysis (PNCC) strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in DU. The PNCC is demonstrated by employing the nanozyme of clinically approved iron oxide nanoparticles coated with a shell of glucose oxidase (Fe3O4-GOx). The Fe3O4-GOx possesses intrinsic glucose oxidase (GOx), catalase (CAT) and peroxidase (POD)-like activities, and can catalyze pH-switchable glucose-initiated GOx/POD and GOx/CAT cascade reaction in acidic and neutral environment, respectively. Specifically, the GOx/POD cascade reaction generating consecutive fluxes of toxic hydroxyl radical spatially targets the acidic biofilm (pH ~ 5.5), and eradicates biofilm to shorten the inflammatory phase and initiate normal wound healing processes. Furthermore, the GOx/CAT cascade reaction producing consecutive fluxes of oxygen spatially targets the neutral wound tissue, and accelerates the proliferation and remodeling phases of wound healing by addressing the issues of hyperglycemia, hypoxia, and excessive oxidative stress. The shortened inflammatory phase temporally coupled with accelerated proliferation and remodeling phases significantly speed up the normal orchestrated wound-healing cascades. Remarkably, this Fe3O4-GOx-instructed spatial–temporal remodeling of DU microenvironment enables complete re-epithelialization of biofilm-infected wound in diabetic mice within 15 days while minimizing toxicity to normal tissues, exerting great transformation potential in clinical DU management. The proposed PNCC concept offers a new perspective for complex pathological microenvironment remodeling, and may provide a powerful modality for the treatment of microenvironment-associated diseases. Graphical Abstract

Abstract The emergence of bacterial resistance due to the evolution of microbes under antibiotic selection pressure, and their ability to form biofilm, has necessitated the development of alternative antimicrobial therapeutics. Physical stimulation, as a powerful antimicrobial method to disrupt microbial structure, has been widely used in food and industrial sterilization. With advances in nanotechnology, nanophysical antimicrobial strategies (NPAS) have provided unprecedented opportunities to treat antibiotic‐resistant infections, via a combination of nanomaterials and physical stimulations. In this review, NPAS are categorized according to the modes of their physical stimulation, which include mechanical, optical, magnetic, acoustic, and electrical signals. The biomedical applications of NPAS in combating bacterial infections are systematically introduced, with a focus on their design and antimicrobial mechanisms. Current challenges and further perspectives of NPAS in the clinical treatment of bacterial infections are also summarized and discussed to highlight their potential use in clinical settings. The authors hope that this review will attract more researchers to further advance the promising field of NPAS, and provide new insights for designing powerful strategies to combat bacterial resistance.

Abstract Background Tobacco use is one of the most important risk factors for health, and China is the largest producer and consumer of tobacco in the world. Monitoring and controlling the tobacco epidemic is an important issue. However, the motivation underlying smoking behavior is complex and specific to the individual. The Habit, Reward and Fear Scale (HRFS) is a feasible tool to evaluate this complex motivation. Objectives To validate the psychometric properties of the HRFS Chinese version (HRFS‐C) and to assess the relationship between motivation and smoking behavior. Method We recruited 967 participants through social media and assessed their smoking behavior with three instruments: the Fagerstrom Test for Nicotine Dependence‐Chinese version (FTND‐C), the Questionnaire on Smoking Urges‐Brief Scale‐Chinese version (QSU‐brief‐C), and the HRFS‐C. Ultimately, we retained 700 valid data points. Cronbach's α and split‐half tests were used to evaluate the reliability. Confirmatory factor analysis, Pearson's r and an analysis of variance (ANOVA) were used to evaluate the validity. In addition, linear regression was used to explore the relationship among the three instruments. The HRFS‐C showed good homogeneity (α = 0.965), concurrent validity, and discriminant validity. A significant linear relationship was observed among the FTND‐C, QSU‐brief‐C, and HRFS‐C (p

One key task in virtual screening is to accurately predict the binding affinity (△G) of protein-ligand complexes. Recently, deep learning (DL) has significantly increased the predicting accuracy of scoring functions due to the extraordinary ability of DL to extract useful features from raw data. Nevertheless, more efforts still need to be paid in many aspects, for the aim of increasing prediction accuracy and decreasing computational cost. In this study, we proposed a simple scoring function (called OnionNet-2) based on convolutional neural network to predict △G. The protein-ligand interactions are characterized by the number of contacts between protein residues and ligand atoms in multiple distance shells. Compared to published models, the efficacy of OnionNet-2 is demonstrated to be the best for two widely used datasets CASF-2016 and CASF-2013 benchmarks. The OnionNet-2 model was further verified by non-experimental decoy structures from docking program and the CSAR NRC-HiQ data set (a high-quality data set provided by CSAR), which showed great success. Thus, our study provides a simple but efficient scoring function for predicting protein-ligand binding free energy.

Abstract Objectives Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. Methods All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. Conclusions The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.