Stabilizing atomic Ru species in conjugated sp2 carbon-linked covalent organic framework for acidic water oxidation.

Suppressing the kinetically favorable lattice oxygen oxidation mechanism pathway and triggering the adsorbate evolution mechanism pathway at the expense of activity are the state-of-the-art strategies for Ru-based electrocatalysts toward acidic water oxidation. Herein, atomically dispersed Ru species are anchored into an acidic stable vinyl-linked 2D covalent organic framework with unique crossed π-conjugation, termed as COF-205-Ru. The crossed π-conjugated structure of COF-205-Ru not only suppresses the dissolution of Ru through strong Ru-N motifs, but also reduces the oxidation state of Ru by multiple π-conjugations, thereby activating the oxygen coordinated to Ru and stabilizing the oxygen vacancies during oxygen evolution process. Experimental results including X-ray absorption spectroscopy, in situ Raman spectroscopy, in situ powder X-ray diffraction patterns, and theoretical calculations unveil the activated oxygen with elevated energy level of O 2p band, decreased oxygen vacancy formation energy, promoted electrochemical stability, and significantly reduced energy barrier of potential determining step for acidic water oxidation. Consequently, the obtained COF-205-Ru displays a high mass activity with 2659.3 A g-1, which is 32-fold higher than the commercial RuO2, and retains long-term durability of over 280 h. This work provides a strategy to simultaneously promote the stability and activity of Ru-based catalysts for acidic water oxidation.

Increased circulating polymorphonuclear myeloid-derived suppressor cells are associated with prognosis of metastatic castration-resistant prostate cancer.

Introduction: Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators. Methods: We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival. Results: The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10-5 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m2 (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05-11.56, P = 0.042). Discussion: PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression.

Nicotinamide adenine dinucleotide treatment confers resistance to neonatal ischemia and hypoxia: effects on neurobehavioral phenotypes.

JOURNAL/nrgr/04.03/01300535-202412000-00031/figure1/v/2024-04-08T165401Z/r/image-tiff Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy. Currently, there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury. Here, we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide, which can protect against hypoxic injury in adulthood, in a mouse model of neonatal hypoxic-ischemic brain injury. In this study, nicotinamide adenine dinucleotide (5 mg/kg) was intraperitoneally administered 30 minutes before surgery and every 24 hours thereafter. The results showed that nicotinamide adenine dinucleotide treatment improved body weight, brain structure, adenosine triphosphate levels, oxidative damage, neurobehavioral test outcomes, and seizure threshold in experimental mice. Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice. Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine (or cysteine) peptidase inhibitor, clade A, member 3N, fibronectin 1, 5'-nucleotidase, cytosolic IA, microtubule associated protein 2, and complexin 2. Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways (e.g., nuclear factor-kappa B, mitogen-activated protein kinase, and phosphatidylinositol 3 kinase/protein kinase B). These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

Establishment and clinical application of the HLA genotype database of platelet-apheresis donors in Suzhou.

The establishment of a platelet-apheresis donor database may provide a feasible solution to improve the efficacy of platelet transfusion in patients with immune platelet transfusion refractoriness (PTR). This study aimed to establish HLA genotype database in Suzhou, to provide HLA-I compatible platelets for PTR patients to ensure the safety and effectiveness of platelet transfusions. We used a polymerase chain reaction sequence-based typing (PCR-SBT) method to establish the database by performing high-resolution HLA-A, -B, and -C genotyping on 900 platelet-apheresis donors. HLA-I antibody was detected in patients using a Luminex device, and HLA-I gene matching was performed by an HLA-Matchmaker. We found that the highest frequency of the HLA-A allele was A*11:01 (17.06 %), followed by A*24:02 (14.67 %) and A*02:01 (13.61 %). The highest frequency of the HLA-B allele was B*46:01 (9.78 %), followed by B*40:01 (8.39 %) and B*13:02 (33 %). After the detection of platelet antibodies in 74 patients with immune PTR, we found 30 HLA-A antibodies and 48 HLA-B antibodies, and there were a variety of high frequency antibodies whose alleles were low in the donor database, such as HLA-A*68:02, and B*57:01. After avoiding donor-specific antibodies (DSA) matching, 102 of 209 platelet-compatible transfusions were effective, resulting in an effective rate of 48.8 %, which significantly improved the efficacy of platelet transfusion. The establishment of a platelet donor database is of great significance to improve the therapeutic effect of platelet transfusion in patients with hematologic disorder, and save blood resources, and it is also the premise and guarantee of precise platelet transfusion.

High-Throughput CD36 Phenotyping on Human Platelets Based on Sandwich ELISA and Mutant Gene Analysis.

Background: CD36 deficiency is closely associated with fetal/neonatal alloimmune thrombocytopenia, platelet transfusion refractoriness, and other hemorrhage disorders, particularly in Asian and African populations. There is a clinical need for rapid and high-throughput methods of platelet CD36 (pCD36) phenotyping to improve the availability of CD36 typing of donors and assist clinical blood transfusions for patients with anti-CD36 antibodies. Such methods can also support the establishment of databases of pCD36-negative phenotypes. Study Design and Methods: A sandwich enzyme-linked immunosorbent assay (ELISA) for CD36 phenotyping of human platelets was developed using anti-CD36 monoclonal antibodies. The reliability of the assay was evaluated by calculating the intra-assay and inter-assay coefficients of variation (CV). A total of 1,691 anticoagulant whole blood samples from healthy blood donors were randomly selected. PCD36 expression was measured using a sandwich ELISA. PCD36 deficiency was confirmed by flow cytometry (FC). Mutations underlying pCD36 deficiency were identified using polymerase chain reaction sequence-based typing (PCR-SBT). Results: The sandwich ELISA for pCD36 phenotyping had high reliability (intra-assay CV, 2.1-4.8%; inter-assay CV, 2.3-5.2%). The sandwich ELISA was used to screen for CD36 expression on platelets isolated from 1,691 healthy blood donors. Of these, 36 samples were pCD36-negative. FC demonstrated absence of CD36 expression on monocytes in three of the 36 cases. In the present study population, the frequency of CD36 deficiency was 2.13% (36/1,691), of which 0.18% (3/1,691) was type I deficiency and 1.95% (33/1,691) was type II deficiency. In addition, we used PCR-SBT to characterize the gene mutations in exons 3-14 of the CD36 gene in 27 cases of CD36 deficiency and discovered 10 types of mutations in 13 pCD36-negative samples. Conclusion: The present study describes the development and characterization of a highly reliable sandwich ELISA for high-throughput screening for pCD36 expression. This novel method is feasible for clinical applications and provides a useful tool for the establishment of databases of pCD36-negative phenotype donors.

A self-centering and stiffness-controlled MEMS accelerometer.

This paper presents a high-performance MEMS accelerometer with a DC/AC electrostatic stiffness tuning capability based on double-sided parallel plates (DSPPs). DC and AC electrostatic tuning enable the adjustment of the effective stiffness and the calibration of the geometric offset of the proof mass, respectively. A dynamical model of the proposed accelerometer was developed considering both DC/AC electrostatic tuning and the temperature effect. Based on the dynamical model, a self-centering closed loop is proposed for pulling the reference position of the force-to-rebalance (FTR) to the geometric center of DSPP. The self-centering accelerometer operates at the optimal reference position by eliminating the temperature drift of the readout circuit and nulling the net electrostatic tuning forces. The stiffness closed-loop is also incorporated to prevent the pull-in instability of the tuned low-stiffness accelerometer under a dramatic temperature variation. Real-time adjustments of the reference position and the DC tuning voltage are utilized to compensate for the residue temperature drift of the proposed accelerometer. As a result, a novel controlling approach composed of a self-centering closed loop, stiffness-closed loop, and temperature drift compensation is achieved for the accelerometer, realizing a temperature drift coefficient (TDC) of approximately 7 µg/°C and an Allan bias instability of less than 1 µg.

A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing.

Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.

Energy and Mass Matching Characteristics of the Heat-Absorbing Side of the Ammonia Energy Storage System under Nonuniform Energy Flow Density.

Ammonia thermochemical energy storage is based on a reversible reaction and realizes energy storage and utilization by absorbing and releasing heat. Under different energy flow densities, the efficiency of an ammonia reactor composed of multiple ammonia reaction tubes is different. Based on the coupling model of light, heat, and chemical energy of an ammonia decomposition reaction system, taking a 20 MW solar thermal power plant as the research object, this paper proposes a new model of ammonia energy storage system, which places the ammonia decomposition side in a low-pressure environment and the ammonia synthesis side in a high-pressure environment. The effects of different inlet temperatures, inlet flow rates, flow distribution, and energy flow density distribution on the ammonia energy storage system were studied. The results show that the increase of inlet temperature and the decrease of inlet flow rate are beneficial to the improvement of thermal efficiency and exergy efficiency of the system to a certain extent, but when the inlet temperature increases or the inlet flow rate decreases to a certain extent, the efficiency of the system will decline. Under the condition of nonuniform energy flow density and nonuniform inlet flow distribution, more ideal system thermal efficiency and exergy efficiency can be obtained.

Cancer trends and risk factors in China over the past 30 years (1990-2019).

Objective: We retrospectively studied cancer mortality and incidence in China from 1990 to 2019, investigated the cancer trends and risk factors, and analyzed the effects of Gross Domestic Product (GDP) on cancer mortality and incidence. Methods: Data was obtained in "Our world in data" in October 2022 to explore mortality rates of different cancers and their trends and the roles of cancer risk factors, including GDP, air pollution, etc. Results: Over the past 30 years, cancer had been China's second leading cause of death. Tracheal, bronchial, and lung cancers, with an annual growth rate of 6.5%, were the most frequently diagnosed cancers. The burden of different cancers changed as the mortality rate of cancer changed. The age-standardized cancer mortality rate had decreased by 19.0%; cancer deaths in all age groups had increased. While the number of cancer deaths in the elderly aged ≥70 did not increase distinctively, its percentage increased by 52.1% and 1.7% annually. The percentage of patients with new-onset cancer increased by 240% and 8.6% annually. For every USD 1,000 increase in GDP, cancer deaths decreased by 2.3/100,000. Tobacco, meat, and alcohol consumption and BMI had increased and were not conducive to the future control of cancer. Conclusions: We summarized the incidence and mortality of major cancers and their trends in China over the past 30 years and analyzed the effects of GDP and the roles of cancer risk factors. Overall GDP growth and effective control of air pollution reduced cancer mortality, while population aging, smoking, alcohol consumption, BMI increasing, and meat consumption brought challenges for cancer control.

Analysis of survival and prognostic factors of clear cell adenocarcinoma of the prostate: a case-control study for a rare cancer entity.

Clear cell adenocarcinoma of the prostate (CCPC) is a rare entity compared to acinar carcinoma of the prostate (APC). The survival rate and prognostic factors of CCPC are still unclear and deserve further study. We downloaded data on prostate cancer from the Surveillance, Epidemiology, and End Results database for 1975-2019. After inclusion and exclusion criteria, we compared APC and analyzed cancer-specific mortality (CSM) and overall mortality (OM) in CCPC patients and prognostic risk factors using a propensity score matching (PSM) study and multivariate Cox regression. We included 408,004 cases of APC as a control group and 130 cases of CCPC as a case group. Compared with APC patients, the incidence of CCPC was extremely low, and the median age of diagnosis was older (72.00 years vs. 69.00 years, p < 0.01). In addition, more rates were diagnosed at an earlier stage (1975-1998, 93.1% vs. 50.2%, p < 0.001), more unstaged or unknown stage ratios (87.7% vs. 42.7%, p < 0.001), and more surgical treatments (66.2% vs. 47.6%, p < 0.001), but the prognosis of CCPC patients was worse. After PSM, the median survival time of CCPC patients was shorter (57.50 month vs. 88.00 month, p < 0.01), the rate of CSM was higher (41.5% vs. 27.7%, p < 0.05), and the rate of OM was higher (99.2% vs. 90.8%, p < 0.01). In the adjusted model 2 after PSM, the CSM risk of CCPC patients reached HR 1.76 (95%CI 1.13-2.72), which was 76% higher than that of APC patients (p < 0.05). It was further found that surgical treatment might benefit CSM in CCPC patients (HR 0.39, 95%CI 0.18-0.82, p < 0.05) in Univariate analysis, but it was insignificant in further multivariate analysis. This is the first large-scale case-control report on the survival risk and prognostic factors of CCPC patients. We found that the prognosis of CCPC patients was significantly worse than that of APC. Surgery might be an effective treatment that may improve its prognosis. Clear cell adenocarcinoma, prostate, acinar carcinoma, survival rate, rare cancer, propensity score matching, case-control study.

Mutations to the BTN2A1 Linker Region Impact Its Homodimerization and Its Cytoplasmic Interaction with Phospho-Antigen-Bound BTN3A1.

Intracellular binding of small-molecule phospho-Ags to the HMBPP receptor complex in infected cells leads to extracellular detection by T cells expressing the Vγ9Vδ2 TCR, a noncanonical method of Ag detection. The butyrophilin proteins BTN2A1 and BTN3A1 are part of the complex; however, their precise roles are unclear. We suspected that BTN2A1 and BTN3A1 form a tetrameric (dimer of dimers) structure, and we wanted to probe the importance of the BTN2A1 homodimer. We analyzed mutations to human BTN2A1, using internal domain or full-length BTN2A1 constructs, expressed in Escherichia coli or human K562 cells, that might disrupt its structure and/or function. Although BTN2A1 is a disulfide-linked homodimer, mutation of cysteine residues C247 and C265 did not affect the ability to stimulate T cell IFN-γ production by ELISA. Two mutations of the juxtamembrane region (at EKE282) failed to impact BTN2A1 function. In contrast, single point mutations (L318G and L325G) near the BTN2A1 B30.2 domain blocked phospho-Ag response. Size exclusion chromatography and nuclear magnetic resonance (NMR) experiments showed that the isolated BTN2A1 B30.2 domain is a homodimer, even in the absence of its extracellular and transmembrane region. [31P]-NMR experiments confirmed that HMBPP binds to BTN3A1 but not BTN2A1, and binding abrogates signals from both phosphorus atoms. Furthermore, the BTN2A1 L325G mutation but not the L318G mutation prevents both homodimerization of BTN2A1 internal domain constructs in size exclusion chromatography (and NMR) experiments and their binding to HMBPP-bound BTN3A1 in isothermal titration calorimetry experiments. Together, these findings support the importance of homodimerization within the BTN2A1 internal domain for phospho-Ag detection.

Electric-Double-Layer Origin of the Kinetic pH Effect of Hydrogen Electrocatalysis Revealed by a Universal Hydroxide Adsorption-Dependent Inflection-Point Behavior.

The mechanism of the kinetic pH effect in hydrogen electrocatalysis, that is, the order-of-magnitude kinetic gap between the hydrogen oxidation and evolution reactions (HOR/HER) in acidic and alkaline electrolytes, has been drastically explored but still intractable to reach a consensus, which severely limits the catalyst advance for alkaline-based hydrogen energy technologies. Herein, the HOR/HER kinetics on a number of precious metal-based electrocatalysts are evaluated in electrolytes with pHs spanning a wide range from 1 to 13. Instead of a monotonous decrease with pH as generally believed, we surprisingly find a universal inflection-point behavior in the pH dependence of HOR/HER kinetics on these catalysts, with both the inflection-point pH and the acid-alkaline activity gap depending on the hydroxide binding energy of the catalyst. Based on a triple-path microkinetic model, in which hydronium (H3O+) and water (H2O) with and without formation of adsorbed hydroxide (OHad), respectively, act as hydrogen donors participating in HOR/HER in various pHs, we reveal that the formation of OHad should promote the HOR/HER kinetics mainly by improving the hydrogen-bond network in the electric double layer (EDL), rather than merely through modulating the energetics of surface reaction steps such as disassociation/formation of water. The present results and conclusions indicate that it is the interfacial EDL that dominates the substantial kinetic pH effects of hydrogen electrocatalysis.

Division of labor and cooperation between different butyrophilin proteins controls phosphoantigen-mediated activation of human γδ T cells.

Butyrophilin (BTN)-3A and BTN2A1 molecules control TCR-mediated activation of human Vγ9Vδ2 T-cells triggered by phosphoantigens (PAg) from microbes and tumors, but the molecular rules governing antigen sensing are unknown. Here we establish three mechanistic principles of PAg-action. Firstly, in humans, following PAg binding to the BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the V-domain of BTN3A2/BTN3A3. Moreover, PAg/B30.2 interaction, and the critical γδ-T-cell-activating V-domain, localize to different molecules. Secondly, this distinct topology as well as intracellular trafficking and conformation of BTN3A heteromers or ancestral-like BTN3A homomers are controlled by molecular interactions of the BTN3 juxtamembrane region. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and division of labor in BTN proteins deepens understanding of PAg sensing and elucidates a mode of action potentially applicable to other BTN/BTNL family members.

Hydroxyl-Binding Energy-Induced Kinetic Gap Narrowing between Acidic and Alkaline Hydrogen Oxidation Reaction on Intermetallic Ru3 Sn7 Catalyst.

Developing highly efficient catalysts toward alkaline hydrogen oxidation reaction (HOR) and narrowing the kinetic gap between acidic and alkaline electrolytes are of great importance for the practical application of alkaline exchange membrane fuel cell . Herein, ordered Ru3 Sn7 /C intermetallic compound has been developed for the HOR under alkaline and acidic conditions. The authors demonstrate that the ordered intermetallic Ru3 Sn7 /C shows much enhanced HOR activity, stability, and CO-tolerance compared with its disordered RuSn solid solution alloy counterpart. More importantly, the authors find that the kinetic gap of HOR between acidic and alkaline media is significantly narrowed in the as-synthesized intermetallic Ru3 Sn7 /C catalysts. Combined experiment results and theoretical calculations, the authors understand that promoted hydroxyl-binding energy on Ru3 Sn7 /C derived from the intermetallic-induced strong electron interaction is responsible for the accelerated alkaline HOR performance and narrowed kinetic gap.

The Role of Discrepant Reactive Intermediates on Ru-Ru2 P Heterostructure for pH-Universal Hydrogen Oxidation Reaction.

Developing highly efficient electrocatalysts for hydrogen oxidation reaction (HOR) under alkaline media is essential for the commercialization of alkaline exchange membrane fuel cell (AEMFC). However, the kinetics of HOR in alkaline media is complicated, resulting in orders of magnitude slower than that in acid, even for the state-of-the-art Pt/C. Here, we find that Ru-Ru2 P/C heterostructure shows HOR performance with a non-monotonous variation in a whole pH region. Unexpectedly, an inflection point located at pH≈7 is observed, showing an anomalous behavior that HOR activity under alkaline media surpasses acidic media. Combining experimental results and theoretical calculations, we propose the roles of discrepant reactive intermediates for pH-universal HOR, while H* and H2 O* adsorption strengths are responsible for acidic HOR, and OH* adsorption strength is essential for alkaline HOR. This work not only sheds light on fundamentally understanding the mechanism of HOR but also provides new designing principles for pH-targeted electrocatalysts.

Effect of high-intensity training on bone mineral density in basketball players / Efeito do treinamento de alta intensidade na densidade mineral óssea em jogadores de basquete / Efecto del entrenamiento de alta intensidad sobre la densidad mineral ósea en jugadores de baloncesto

ABSTRACT Introduction Increasing the bone mineral density of athletes can provide better basic physical conditions for basketball players, prevent fractures caused by osteopenia and reduce the occurrence of serious sports injuries. Objective Explore the effect of high-intensity training on bone mineral density in basketball players. Methods In this experiment, 30 subjects were divided into male and female groups, and high-intensity exercise training was performed for 60 minutes, three times a week, for eight weeks. The relevant indices were measured before and after training, and their data were classified and analyzed. Results High-intensity training can significantly improve the bone mineral density of basketball players, and the increase of bone mineral density of female basketball players is slightly lower than that of male players. In addition, the increase in bone mineral density can comprehensively improve athletes' muscular strength and physical fitness. Conclusion High-intensity training can improve basketball players' bone mineral density and sports skills, requiring promoting studies for its popularization in colleges and universities. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Aumentar o nível de densidade mineral óssea dos atletas pode proporcionar melhores condições físicas básicas para jogadores de basquetebol, prevenir fraturas causadas pela osteopenia e reduzir a ocorrência de lesões esportivas graves. Objetivo Explorar o efeito do treinamento de alta intensidade na densidade mineral óssea de jogadores de basquetebol. Métodos Neste experimento, 30 indivíduos foram divididos em grupo masculino e feminino, o treinamento de exercícios de alta intensidade foi realizado por 60 minutos, três vezes por semana durante um total de 8 semanas. Os índices relevantes foram medidos antes e após o treinamento, seus dados foram classificados e analisados. Resultados O treinamento de alta intensidade pode melhorar significativamente a densidade mineral óssea dos jogadores de basquetebol, e o aumento da densidade mineral óssea das jogadoras de basquetebol feminino é ligeiramente menor do que o dos jogadores masculinos. Além disso, o aumento da densidade mineral óssea pode melhorar de forma abrangente a força muscular e a aptidão física dos atletas. Conclusão O treinamento de alta intensidade pode promover a melhoria da densidade mineral óssea e habilidades esportivas dos jogadores de basquetebol, necessitando de estudos promotores para sua popularização em Faculdades e Universidades. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción Aumentar el nivel de densidad mineral ósea de los deportistas puede proporcionar mejores condiciones físicas básicas a los jugadores de baloncesto, prevenir las fracturas causadas por la osteopenia y reducir la aparición de lesiones deportivas graves. Objetivo Explorar el efecto del entrenamiento de alta intensidad sobre la densidad mineral ósea en jugadores de baloncesto. Métodos En este experimento, 30 sujetos se dividieron en el grupo de hombres y mujeres, se realizó un entrenamiento de ejercicios de alta intensidad durante 60 minutos, tres veces por semana durante un total de 8 semanas. Se midieron los índices relevantes antes y después del entrenamiento, se clasificaron sus datos y se analizaron. Resultados El entrenamiento de alta intensidad puede mejorar significativamente la densidad mineral ósea de los jugadores de baloncesto, y el aumento de la densidad mineral ósea de las jugadoras de baloncesto es ligeramente inferior al de los jugadores. Además, el aumento de la densidad mineral ósea puede mejorar ampliamente la fuerza muscular y la forma física de los deportistas. Conclusión El entrenamiento de alta intensidad puede promover la mejora de la densidad mineral ósea y de las habilidades deportivas en los jugadores de baloncesto, siendo necesario promover estudios para su popularización en Colegios y Universidades. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Correlation between Laboratory-Accelerated Corrosion and Field Exposure Test for High-Strength Stainless Steels.

Equipment in a long-term marine atmosphere environment is prone to corrosion failure. Natural field exposure tests usually require a long time to obtain corrosion information. This study worked out a laboratory-accelerated corrosion test method that has a strong correlation with the natural environment test in Wanning, Hainan, and can be used as the basis for life assessment and the prediction of two high-strength stainless-steel materials. The mathematical model of corrosion weight loss of two high-strength stainless steels (3Cr13 and 00Cr12Ni10MoTi) was established by a field exposure test and a laboratory-accelerated corrosion test. Then, the correlation between the field exposure test and the laboratory-accelerated corrosion test was evaluated using qualitative and quantitative methods, and the acceleration ratio was calculated using the accelerated switching factor (ASF) method. The results show that: (1) The corrosion morphology of the two stainless steels after 15 days of laboratory-accelerated corrosion testing is similar to that obtained after two years of field exposure. (2) The value of gray correlation between the laboratory-accelerated corrosion test and the field exposure test is not less than 0.75. (3) The acceleration ratio of both stainless steels increases with the corrosion test time in the laboratory. The corrosion prediction models for the two stainless steels are T3Cr13 = 6.234 t1.634 and T00Cr12Ni10MoTi = 55.693 t1.322, respectively.

New Technologies Bloom Together for Bettering Cancer Drug Conjugates.

Drug conjugates, including antibody-drug conjugates, are a step toward realizing Paul Ehrlich's idea from over 100 years ago of a "magic bullet" for cancer treatment. Through balancing selective targeting molecules with highly potent payloads, drug conjugates can target specific tumor microenvironments and kill tumor cells. A drug conjugate consists of three parts: a targeting agent, a linker, and a payload. In some conjugates, monoclonal antibodies act as the targeting agent, but new strategies for targeting include antibody derivatives, peptides, and even small molecules. Linkers are responsible for connecting the payload to the targeting agent. Payloads impact vital cellular processes to kill tumor cells. At present, there are 12 antibody-drug conjugates on the market for different types of cancers. Research on drug conjugates is increasing year by year to solve problems encountered in conjugate design, such as tumor heterogeneity, poor circulation, low drug loading, low tumor uptake, and heterogenous expression of target antigens. This review highlights some important preclinical research on drug conjugates in recent years. We focus on three significant areas: improvement of antibody-drug conjugates, identification of new conjugate targets, and development of new types of drug conjugates, including nanotechnology. We close by highlighting the critical barriers to clinical translation and the open questions going forward. SIGNIFICANCE STATEMENT: The development of anticancer drug conjugates is now focused in three broad areas: improvements to existing antibody drug conjugates, identification of new targets, and development of new conjugate forms. This article focuses on the exciting preclinical studies in these three areas and advances in the technology that improves preclinical development.

Ligand-induced interactions between butyrophilin 2A1 and 3A1 internal domains in the HMBPP receptor complex.

The ligand-bound (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) receptor (BTN3A1 and BTN2A1) is detectable by the T cell receptor (TCR) of Vγ9Vδ2 T cells. Although BTN3A1 binds to phosphoantigens (pAgs), the mechanisms resulting in receptor activation are not clear. We used CRISPR-Cas9, ELISA, nano-bioluminescence resonance energy transfer (BRET), and isothermal titration calorimetry (ITC) to evaluate the role of BTN2A1. Depletion of BTN2A1 and rescue experiments demonstrate that its internal domain is essential for pAg detection. Internal hetero-BRET signals are observed between BTN2A1 and BTN3A1 that are increased by pAg. ITC detects a direct interaction between the intracellular domains of BTN3A1 and BTN2A1 only in the presence of pAg. This interaction is abrogated by removal of the BTN2A1 juxtamembrane (JM) region but not by removal of the BTN3A1 JM region. Regional mutations between BTN2A1 316-326 clearly affect the interferon γ (IFNγ) response and hetero-BRET signal. Mutations to amino acids L318, W320, and L325 indicate that these amino acids are crucial. This study demonstrates a pAg-inducible interaction between BTN2A1 and BTN3A1 internal domains.