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The three-year COVID-19 pandemic ‘has’ caused a wide range of medical, social, political, and financial implications. Since the end of 2020, various mutations and variations in SARS-CoV-2 strains, along with the immune escape phenomenon, have emerged. There is an urgent need to identify a relatively stable target for the development of universal vaccines and drugs that can effectively combat both SARS-CoV-2 strains and their mutants. Currently, the main focus in treating SARS-CoV-2 lies in disrupting the virus’s life cycle. The main protease (Mpro) is closely associated with virus replication and maturation and plays a crucial role in the early stages of infection. Consequently, it has become an important target for the development of SARS-CoV-2-specific drugs. This review summarizes the recent research progress on the novel coronavirus’s main proteases, including the pivotal role of Mpro in the virus’s life cycle, the structure and catalytic mechanism of Mpro, the self-maturation mechanism of Mpro, the role of Mpro in virus immune escape, the current methods of developing antiviral drugs targeting Mpro, and the key drugs that have successfully entered clinical trials. The aim is to provide researchers involved in the development of antiviral drugs targeting Mpro with systematic and comprehensive information.

Background Soil water content is one of the critical indicators in agricultural systems. Visible/near-infrared hyperspectral remote sensing is an effective method for soil water estimation. However, noise removal from massive spectral datasets and effective feature extraction are challenges for achieving accurate soil water estimation using this technology. Methods This study proposes a method for hyperspectral remote sensing soil water content estimation based on a combination of continuous wavelet transform (CWT) and competitive adaptive reweighted sampling (CARS). Hyperspectral data were collected from soil samples with different water contents prepared in the laboratory. CWT, with two wavelet basis functions (mexh and gaus2), was used to pre-process the hyperspectral reflectance to eliminate noise interference. The correlation analysis was conducted between soil water content and wavelet coefficients at ten scales. The feature variables were extracted from these wavelet coefficients using the CARS method and used as input variables to build linear and non-linear models, specifically partial least squares (PLSR) and extreme learning machine (ELM), to estimate soil water content. Results The results showed that the correlation between wavelet coefficients and soil water content decreased as the decomposition scale increased. The corresponding bands of the extracted wavelet coefficients were mainly distributed in the near-infrared region. The non-linear model (ELM) was superior to the linear method (PLSR). ELM demonstrated satisfactory accuracy based on the feature wavelet coefficients of CWT with the mexh wavelet basis function at a decomposition scale of 1 (CWT(mexh_1)), with R2, RMSE, and RPD values of 0.946, 1.408%, and 3.759 in the validation dataset, respectively. Overall, the CWT(mexh_1)-CARS-ELM systematic modeling method was feasible and reliable for estimating the water content of sandy clay loam.

All-trans retinoic acid (ATRA) plays a role in tissue development, neural function, reproduction, vision, cell growth and differentiation, tumor immunity, and apoptosis. ATRA can act by inducing autophagic signaling, angiogenesis, cell differentiation, apoptosis, and immune function. In the blood system ATRA was first used with great success in acute promyelocytic leukemia (APL), where ATRA differentiated leukemia cells into mature granulocytes. ATRA can play a role not only in APL, but may also play a role in other hematologic diseases such as immune thrombocytopenia (ITP), myelodysplastic syndromes (MDS), non-APL acute myeloid leukemia (AML), aplastic anemia (AA), multiple myeloma (MM), etc., especially by regulating mesenchymal stem cells and regulatory T cells for the treatment of ITP. ATRA can also increase the expression of CD38 expressed by tumor cells, thus improving the efficacy of daratumumab and CD38-CART. In this review, we focus on the mechanism of action of ATRA, its role in various hematologic diseases, drug combinations, and ongoing clinical trials.

Globally, breast cancer stands as the most prevalent form of cancer among women. The tumor microenvironment of breast cancer often exhibits hypoxia. Hypoxia-inducible factor 1-alpha, a transcription factor, is found to be overexpressed and activated in breast cancer, playing a pivotal role in the anoxic microenvironment by mediating a series of reactions. Hypoxia-inducible factor 1-alpha is involved in regulating downstream pathways and target genes, which are crucial in hypoxic conditions, including glycolysis, angiogenesis, and metastasis. These processes significantly contribute to breast cancer progression by managing cancer-related activities linked to tumor invasion, metastasis, immune evasion, and drug resistance, resulting in poor prognosis for patients. Consequently, there is a significant interest in Hypoxia-inducible factor 1-alpha as a potential target for cancer therapy. Presently, research on drugs targeting Hypoxia-inducible factor 1-alpha is predominantly in the preclinical phase, highlighting the need for an in-depth understanding of HIF-1α and its regulatory pathway. It is anticipated that the future will see the introduction of effective HIF-1α inhibitors into clinical trials, offering new hope for breast cancer patients. Therefore, this review focuses on the structure and function of HIF-1α, its role in advancing breast cancer, and strategies to combat HIF-1α-dependent drug resistance, underlining its therapeutic potential.

Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.

In order to uniformly disperse the ceramic reinforcements synthesized in-situ in the copper matrix composites, this study used Carbon Polymer Dot (CPD) as the carbon source and Cu–1.0%Ti alloy powder as the matrix for supplying Ti source to prepare in-situ synthesized TiC/Cu composites. The results show that TiC nano-precipitates, having the similar particle sizes with the CPD, form at the grains interior and grain boundaries, and maintain a uniform distribution state. Compared with the matrix, 0.3 ​wt% CPD/Cu composite displays the best strength-plastic compatibility, the ultimate tensile strength achieves 385 ​MPa accompanied with a corresponding elongation of 21%, owing to the dislocation hindrance caused by nano-carbide and excellent interface bonding between nano TiC and the Cu matrix. The density function theory calculation supports our experimental results by showing a tighter and stronger interface contact. This work presents a new approach for studying in-situ carbide precipitates.

Background: In this study, an investigation was conducted on clinical drug trials comprising pregnant women in China that provided data on the quantity, properties, source of funding, and geographical distribution regarding registration and post-marketing studies.Methods: We conducted a cross-sectional descriptive study of clinical trials of pregnant women in China on 30 December 2021, and it was registered on the official Drug Clinical Trial Information Management Platform (ChiCTR) (http://www.chinadrugtrials.org.cn) established by the State Food and Drug Administration of China (Chinese FDA).Results: This study encompassed 72 registered trials (0.46%, 72/15,539) for data analysis. Of these trials, 43.1% of trials were started between 2013 and 2016, and nearly half of the trials (48.6%) were completed. Industries were listed as the primary sponsor for 95.8% trials. Economically developed eastern China and northern China, accounting for 69.5% of the 72 registered trials, were the most frequently identified study locations. Regarding study designs of these trials, more than half of the trials (70.8%) were randomized, 61.1% were a parallel assignment, 33.3% were phase 3, and half of the trials (54.2%) were open label. In total, 23 trials met the requirements after excluding trials of cancer and/or of postmenopausal women, accounting for 0.15% of the 15,539 registered trials in the ChiCTR websites. Of the 72 clinical trials, 54 drugs for 18 indications were included. Of these indications, the highest proportion of the trials is osteoporosis (27.8%), followed by cancer (22.2%), assisted reproduction (13.9%), and other indications (13.9%).Conclusion: This survey revealed a significant shortage of the development, evaluation, and safety trials of pregnancy-related drugs in China. Modifying or adding legislation and providing financial incentives may therefore encourage pharmaceutical companies to conduct additional clinical trials on pregnant women.

FeF2/carbon composite nanoparticle was prepared by a one-pot thermal reaction using a mixture of ferrous oxalate and PTFE as precursor. FeF2 was obtained as the main phase according to the XRD patterns of the samples prepared in the present study. Furthermore, the FeF2 particle has a size of 50–100 nm. Its electrochemical properties were studied in the 4.2–1.3 V region at a current density of 60 mA g−1. It exhibited an initial discharge capacity of 503.394 mA h g−1 and still reserved discharge capacity of about 268.478, 211.34, 193.817 and 183.328 mA h g−1 at the 2nd, 3rd, 10th, and 20th cycles, respectively. Keywords: Lithium-ion battery, FeF2, Nanoparticles, Cathode material, Charge–discharge performance

This study aimed to investigate the ability of chelerythrine chloride (CHE), the main active ingredient of Macleaya cordata, to induce apoptosis in human gastric cancer BGC-823 cells. The results demonstrate that CHE inhibits cell proliferation in a time- and dose-dependent manner with accompanying S phase arrest. It also induces apoptosis by a mechanism involving a reduction in the mitochondrial membrane potential, the release of cytochrome c, activation of caspase 3 and cleavage of poly-ADP-ribose polymerase. In addition, CHE-induced apoptosis is accompanied by down-regulation of Bcl-xl and Bcl-2 proteins with no change in the levels of Bax proteins. Taken together, the results support the development of CHE as a potentially useful anticancer drug for the treatment of gastric cancer.

Sodium-ion batteries have become one of the most promising options for large-scale energy storage due to their abundant sodium source, high storage capacity and relatively low price. Among the key components of sodium-ion batteries, cathode materials play a pivotal role and have a significant impact on the energy density and power density of the battery. Advances in cathode materials ultimately determine the practical applications of sodium-ion batteries. The P2-type layered transition metal oxides have open Na+ diffusion channels, and Na+ can migrate through the adjacent trigonal positions, resulting in high diffusion coefficients, giving them good rate and cyclic properties. However, in P2-type layered transition metal oxide cathode materials, there are several challenges, such as structural distortion, irreversible oxygen atom redox at high voltages, and irreversible phase transitions, which seriously affect the rate and cycling performance of the batteries. As a result, these issues have hindered the widespread application of sodium-ion batteries in largescale energy storage. It is crucial to optimize the P2-NaxTMO2 layered transition metal oxide cathode materials. This review summarizes the challenges and research progress of P2-NaxTMO2 layered transition metal oxide cathode materials for the development of P2-NaxTMO2 cathodes for high-energy sodium-ion batteries. [ABSTRACT FROM AUTHOR]