Cordymin alleviates osteoporosis induced by hindlimb unloading via regulating the gut - microelements -bone axis --for non-clinical studies.

INTRODUCTION: The purpose of this study was to evaluate the protective effects of cordymin on osteoporosis induced by hindlimb unloading(HLU) in rats and whether cordymin can prevent bone loss from HLU. MATERIALS AND METHODS: We employed the hindlimb suspension rats model to mimic physiological changes concomitant with space travel.The mechanical strength in the femoral neck,cancellous bone volume, gut microbiota structure,serum calcium and phosphorus contents, bone mineral content and bone mineral content can be changed after hindlimb unloading. Oral cordymin was administered for 4 weeks,cordymin treatment significantly increased the mechanical strength through elevated bone volume/tissue volume (BV/TV), trabecular number (Tb. N), trabecular thickness (Tb. Th) and decreased trabecular separation (Tb. Sp). RESULTS: Importantly, 16 S rRNA sequencing showed cordymin treatment regulated the various genera that were imbalanced in hindlimb unloading rats. At the same time,The plasma total calcium and inorganic phosphate concentrations in hindlimb unloading rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with cordymin. CONCLUSION: These data indicate that the cordymin might exert bone protective effects indirectly via modulating the complex relationship between gut microbiota, microelements and bone loss.

Ginger polysaccharide promotes myeloid-derived suppressor cell apoptosis by regulating lipid metabolism.

Recently, targeting myeloid-derived suppressor cells (MDSCs) which mainly play an immunosuppressive role in tumor microenvironment has become a hot spot in tumor immunotherapy. This study focuses on biological effect of ginger polysaccharide extracted from natural plants on promoting apoptosis of MDSCs by regulating lipid metabolism. An MTT assay was used to detect the inhibitory effect of ginger polysaccharide on the growth of an MDSC-like cell line (MSC-2). The apoptosis-promoting effect of ginger polysaccharide on MSC-2 cells was detected by flow cytometry. Expression levels of apoptosis proteins (caspase 9 and Bcl-2) and lipid metabolism enzymes (fatty acid synthase (FASN) and diacylglycerol acyltransferase 2) in MSC-2 cells treated with different concentrations of ginger polysaccharide were detected by western blot assay. Nile red staining was used to quantitatively detect the effect of ginger polysaccharide on lipid droplet synthesis. Ginger polysaccharide inhibited proliferation of MSC-2 cells and promoted their apoptosis by upregulating pro-apoptotic caspase 9 protein, downregulating anti-apoptotic Bcl-2 protein, inhibiting expression of FASN and diacylglycerol acyltransferase 2 (key enzymes in fatty acid synthesis and lipid droplet formation, respectively). Ginger polysaccharide promoted apoptosis of MDSCs by regulating key lipid metabolism enzymes, inhibiting fatty acid synthesis and lipid droplet accumulation, and reducing the energy supply of cells.

A highly powerful nonspecific strategy to reduce COVID-19 deaths.

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.

Highly adaptive Phenuiviridae with biomedical importance in multiple fields.

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuivirid species, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and research on phenuiviruses has made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and important virus family and conduct relevant risk analysis.

LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA-AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown. METHODS: The mRNA and protein expression of genes were examined by RT-qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK-8, colony formation, Transwell and spheroid formation assays. The CD44+ and CD166+ -positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull-down assays. The tumor growth was detected through in vivo nude mice assay. RESULTS: The lncRNA PITPNA-AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA-AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA-AS1 absorbed miR-223-3p and that miR-223-3p targeted PTN. MiR-223-3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA-AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA-AS1/miR-223-3p/PTN axis accelerated tumor development in vivo. CONCLUSIONS: It is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA-AS1 in LUSC. The data disclosed that PITPNA-AS1 upregulated PTN through sponging miR-223-3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.

Insecticidal Activity of Four Lignans Isolated from Phryma leptostachya.

A new lignan (T4) and three known lignans (T1, T2, and T3) were isolated from the methanol extract of the roots of Phryma leptostachya using bioassay-guided method, and their structures were identified as phrymarolin I (T1), II (T2), haedoxan A (T3), and methyl 4-((6a-acetoxy-4-(6-methoxybenzo[d][1,3]dioxol-5-yl)tetrahydro-1H,3H-furo[3,4-c]furan-1-yl)oxy)-1-hydroxy-2,2-dimethoxy-5-oxocyclopent-3-ene-1-carboxylate (T4) byNMR and ESI-MS spectral data. Bioassay results revealed that haedoxan A exhibited remarkably high insecticidal activity against Mythimna separata with a stomach toxicity LC50 value of 17.06 mg/L and a topical toxicity LC50 value of 1123.14 mg/L at 24 h, respectively. Phrymarolin I and compound T4 also showed some stomach toxicity against M. separata with KD50 values of 3450.21 mg/L at 4 h and 2807.10 mg/L at 8 h, respectively. In addition, phrymarolin I and haedoxan A exhibited some stomach toxicity against Plutella xylostella with an LC50 value of 1432.05 and 857.28 mg/L at 48 h, respectively. In conclusion, this study demonstrated that lignans from P. leptostachya are promising as a novel class of insecticides or insecticide lead compounds for developing botanical pesticides.

Effects of Celangulin IV and V From Celastrus angulatus Maxim on Na+/K+-ATPase Activities of the Oriental Armyworm (Lepidoptera: Noctuidae).

Na(+)/K(+)-ATPase (sodium pump) is an important target for the development of botanical pesticide as it is responsible for transforming chemical energy in ATP to osmotic work and maintaining electrochemical Na(+ )and K(+ )gradients across the cell membrane of most animal cells. Celangulin IV (C-IV) and V (C-V), which are isolated from the root bark of Celastrus angulatus, are the major active ingredients of this insecticidal plant. The activities of C-IV and C-V on Na(+)/K(+)-ATPase were investigated by ultramicro measuring method to evaluate the effects of C-IV and C-V on Na(+)/K(+)-ATPase activities of the brain from the fifth Mythimna separata larvae and to discuss the insecticidal mechanism of C-IV and C-V. Results indicate that inhibitory activities of Na(+)/K(+)-ATPase by C-IV and C-V possess an obvious concentration-dependent in vitro. Compared with C-IV, the inhibition of C-V on Na(+)/K(+)-ATPase was not striking. In vivo, at a concentration of 25 mg/liter, the inhibition ratio of C-IV on Na(+)/K(+)-ATPase activity from the brain in narcosis and recovery period was more remarkable than that of C-V. Furthermore, the insects were fed with different mixture ratios of C-IV and C-V. The inhibition extent of Na(+)/K(+)-ATPase activity was corresponded with the dose of C-IV. However, C-V had no notable effects. This finding may mean that the mechanism of action of C-IV and C-V on Na(+)/K(+)-ATPase were different. Na(+)/K -ATPase may be an action target of C-IV and C-V.

Non-alcoholic fatty liver disease predicts type 2 diabetes mellitus, but not prediabetes, in Xi'an, China: a five-year cohort study.

BACKGROUND & AIMS: Emerging studies have focused the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM) but the results were inconsistent. In addition, few studies have put focus on the association between NAFLD and the risk of prediabetes. We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM and prediabetes in Chinese population. METHODS: The population-based cohort study held in Xi'an, Northwestern China, was based on China National Diabetes and Metabolic Disorders Survey. During a follow-up of 5 years, 508 healthy subjects were included as study sample. NAFLD was determined by abdominal ultrasonography. T2DM and prediabetes were diagnosed based on oral glucose tolerance test. RESULTS: Of 508 subjects, 97 (19.1%) were diagnosed as NAFLD and 411 (80.9%) were as non-NAFLD; 20 (3.9%) developed diabetes and 85 (16.7%) developed prediabetes during follow-up. The incidence of diabetes and prediabetes in the NAFLD group was 20.6 and 51.6 per 1000 person-years, respectively, whereas that in non-NAFLD group was 4.9 and 29.2 per 1000 person-years respectively. Cox proportional hazard regression showed that the multivariable-adjusted relative risk (RR) of T2DM and prediabetes in the NAFLD group was 4.462 [95% confidence interval (CI): 1.855-10.734, P < 0.001] and 1.642 (95% CI: 0.965-2.793, P = 0.067), respectively, compared with non-NAFLD group. CONCLUSIONS: Non-alcoholic fatty liver disease was a significant predictor for future diabetes, but not for prediabetes, in Xi'an, China. More cohort studies are needed to confirm our findings.

The Guidelines for use and promotion of low sodium salt in China.

AIM: Both excessive intake of sodium and inadequate intake of potassium are associated with blood pressure elevation and subsequent increase in the risk of cardiovascular disease, which accounts for the largest number of deaths in China and worldwide. Low sodium salt, a mixture of mainly sodium chloride and potassium chloride, has shown its great potential as a promising population strategy for sodium intake reduction through multiple large-scale, multicenter, randomized controlled trials among populations including patients with cardiovascular disease, individuals with and without hypertension, older and younger adults, and men and women in China and other countries. This Guidelines aims to provide expert recommendations for promotion and use of low sodium salt in China, based on the current available scientific evidence regarding the effectiveness, safety, cost-effectiveness, and acceptability of low sodium salts in various population groups and different application scenarios. The suggestions to key stakeholders are also made. METHODS: A working group, an expert review committee and an advisory committee were established to be responsible for formulating the guidelines' scope and key questions to be addressed, for searching, synthesizing, and evaluating research evidence, proposing and reviewing the recommendations. The consensus on the final recommendations was reached using the GRADE grid method. RESULTS: The working group summarized current available evidence of salt substitution regarding its effectiveness, safety, cost-effectiveness, acceptability, availability, suitability, etc. The Guidelines provided six recommendations advising different populations how to use low sodium salt, four recommendations on the application of low sodium salts in different scenarios, and five suggestions for key stakeholders to promote salt substitution. CONCLUSION: The first evidence-based guidelines on promotion and use of low sodium salts covers all key questions in relevance and would play a critical role in prevention and control of hypertension and cardiovascular disease in China and worldwide.

ECM-mimetic glucomannan hydrogel promotes pressure ulcer healing by scavenging ROS, promoting angiogenesis and regulating macrophages.

Pressure ulcers (PUs) have emerged as a significant burden on both individuals and society. Effective treatment of PUs is a significant clinical challenge due to the compromised tissue microenvironment characterized by extracellular matrix (ECM) depletion, increased levels of reactive oxygen species (ROS), excessive inflammation and impaired angiogenesis. To this end, we have developed a glucomannan hydrogel (GM-Pgel) that mimics the skin's extracellular matrix to accelerate wound healing by regulating chronic inflammation in the PUs. This hydrogel not only faithfully replicates the components and nanofibrous architecture of ECM-like glycoproteins but also exhibits remarkable capabilities in enhancing neovascularization, scavenging ROS, and promoting macrophage polarization toward the M2 phenotype. In summary, this ECM-mimetic multifunctional hydrogel emerges as a promising dressing with diverse functionalities, capable of reshaping the compromised tissue environment without the need for additional drugs, exogenous cytokines, or cells. This presents a compelling and effective strategy for the repair and regeneration of chronic cutaneous wounds.

Synthetic CT generation from CBCT using double-chain-CycleGAN.

PURPOSE: Cone-beam CT (CBCT) has the advantage of being less expensive, lower radiation dose, less harm to patients, and higher spatial resolution. However, noticeable noise and defects, such as bone and metal artifacts, limit its clinical application in adaptive radiotherapy. To explore the potential application value of CBCT in adaptive radiotherapy, In this study, we improve the cycle-GAN's backbone network structure to generate higher quality synthetic CT (sCT) from CBCT. METHOD: An auxiliary chain containing a Diversity Branch Block (DBB) module is added to CycleGAN's generator to obtain low-resolution supplementary semantic information. Moreover, an adaptive learning rate adjustment strategy (Alras) function is used to improve stability in training. Furthermore, Total Variation Loss (TV loss) is added to generator loss to improve image smoothness and reduce noise. RESULTS: Compared to CBCT images, the Root Mean Square Error (RMSE) dropped by 27.97 from 158.49. The Mean Absolute Error (MAE) of the sCT generated by our model improved from 43.2 to 32.05. The Peak Signal-to-Noise Ratio (PSNR) increased by 1.61 from 26.19. The Structural Similarity Index Measure (SSIM) improved from 0.948 to 0.963, and the Gradient Magnitude Similarity Deviation (GMSD) improved from 12.98 to 9.33. The generalization experiments show that our model performance is still superior to CycleGAN and respath-CycleGAN.

Oxidation treatment of shale gas produced water: Molecular changes in dissolved organic matter composition and toxicity evaluation.

Produced water (PW) is the largest waste stream generated by hydraulic fracturing in an unconventional shale gas reservoir. Oxidation processes (OPs) are frequently used as advanced treatment method in highly complicated water matrix treatments. However, the degradation efficiency is the main focus of research, organic compounds and their toxicity have not been properly explored. Here, we obtained the characterization and transformation of dissolved organic matters of PW samples from the first shale gas field of China by two selected OPs using FT-ICR MS. CHO, CHON, CHOS, and CHONS heterocyclic compounds associated with lignins/CRAM-like, aliphatic/proteins, and carbohydrates compounds were the major organic compounds identified. Electrochemical Fe2+/HClO oxidation preferentially removed aromatic structures, unsaturated hydrocarbons, and tannin compounds with a double-bond equivalence (DBE) value below 7 to more saturated compounds. Nevertheless, Fe (VI) degradation manifested in CHOS compounds with low DBE values, especially single bond compounds. Oxygen- and Sulfur-containing substances, primarily O4-11, S1O3-S1O12, N1S1O4, and N2S1O10 classes, were the main recalcitrant components in OPs. The toxicity assessment showed that the free-radical-formed Fe2+/HClO oxidation could cause significant DNA damage. Therefore, the toxicity response byproducts need spcial attention when conducting OPs. Our results led to discussions on designing appropriate treatment strategies and the development of PW discharge or reuse standards.

Zoonotic Hantaviridae with Global Public Health Significance.

Hantaviridae currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.

Bis(2-amino-5-methyl-1,3,4-thia-diazole-κN(3))dichloridocobalt(II).

In the monomeric title complex, [CoCl(2)(C(3)H(5)N(3)S)(2)], the Co(II) atom is tetra-coordinated by two chloride anions and two N atoms from two monodentate 2-amino-5-methyl-1,3,4-thia-diazole ligands, giving a slightly distorted tetra-hedral stereochemistry [bond angle range about Co = 105.16 (12)-112.50 (10)°]. In the complex, the dihedral angle between the 1,3,4-thia-diazole planes in the two ligands is 72.8 (1)°. There are two intra-molecular N-H⋯Cl inter-actions in the complex unit, while in the crystal, inter-molecular N-H⋯N and N-H⋯Cl hydrogen bonds link these units into a two-dimensional layered structure parallel to (011).

Bis[4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole-κ(2)N(1),N(5)]diaqua-cobalt(II) bis-(perchlorate).

In the title structure, [Co(C(12)H(10)N(6))(2)(H(2)O)(2)](ClO(4))(2), the Co(II) atom lies on an inversion centre and is coordinated in a slightly distorted octa-hedral geometry by four N atoms from two 4-amino-3,5-bis-(pyridin-2-yl)-4H-1,2,4-triazole (adpt) ligands in equatorial positions and two O atoms from two water mol-ecules in axial positions. An intra-molecular N-H⋯N inter-action stabilizes the mol-ecular conformation. Inter-molecular N-H⋯O and O-H⋯O inter-actions involving the perchlorate counter-anions extend the monomeric compound into a two-dimensional network parallel to the bc plane.

Bis[3-(pyrazin-2-yl)-5-(pyridin-2-yl-κN)-1,2,4-triazol-1-ido-κN(1)]copper(II).

In the mononuclear title complex, [Cu(C(11)H(7)N(6))(2)], the Cu(II) atom lies on a crystallographic inversion centre and is coordinated by four N atoms from two bidentate chelate monoanionic 3-(pyrazin-2-yl)-5-(pyridin-2-yl-1,2,4-triazol-1-ido ligands, two from the triazolide rings [Cu-N = 1.969 (2) Å] and two from the pyridine rings [Cu-N = 2.027 (2) Å], giving a slightly distorted square-planar geometry.

Facile synthesis of magnesium-based metal-organic framework with tailored nanostructure for effective volatile organic compounds adsorption.

A novel Mg(II) metal-organic framework (Mg-MOF) was synthesized based on the ligand of 2,2'-bipyridine-4,4'-dicarboxylic acid. Single-crystal X-ray structural analysis confirmed that three-dimensional-nanostructure Mg-MOFs formed a monoclinic system with a channel size of 15.733 Å × 23.736 Å. N2 adsorption isotherm, Fourier transform infrared spectroscopy, thermogravimetric analysis and high-resolution transmission electron microscopy were performed to characterize the thermal stability and purity of the Mg-MOFs. The adsorption studies on four typical volatile organic compounds (VOCs) emitted during wood drying showed that Mg-MOFs have noteworthy adsorption capacities, especially for benzene and ß-pinene with adsorptions of 182.26 mg g-1 and 144.42 mg g-1, respectively. In addition, the adsorption of Mg-MOFs mainly occurred via natural adsorption, specifically, multi-layer physical adsorption, accompanied by chemical forces, which occurred in the pores where the VOCs molecules combined with active sites. As an adsorbent, Mg-MOFs exhibit versatile behaviour for toxic gas accumulation.

Construction of a Novel LncRNA Signature Related to Genomic Instability to Predict the Prognosis and Immune Activity of Patients With Hepatocellular Carcinoma.

Background: Genomic instability (GI) plays a crucial role in the development of various cancers including hepatocellular carcinoma. Hence, it is meaningful for us to use long non-coding RNAs related to genomic instability to construct a prognostic signature for patients with HCC. Methods: Combining the lncRNA expression profiles and somatic mutation profiles in The Cancer Genome Atlas database, we identified GI-related lncRNAs (GILncRNAs) and obtained the prognosis-related GILncRNAs through univariate regression analysis. These lncRNAs obtained risk coefficients through multivariate regression analysis for constructing GI-associated lncRNA signature (GILncSig). ROC curves were used to evaluate signature performance. The International Cancer Genomics Consortium (ICGC) cohort, and in vitro experiments were used for signature external validation. Immunotherapy efficacy, tumor microenvironments, the half-maximal inhibitory concentration (IC50), and immune infiltration were compared between the high- and low-risk groups with TIDE, ESTIMATE, pRRophetic, and ssGSEA program. Results: Five GILncRNAs were used to construct a GILncSig. It was confirmed that the GILncSig has good prognostic evaluation performance for patients with HCC by drawing a time-dependent ROC curve. Patients were divided into high- and low-risk groups according to the GILncSig risk score. The prognosis of the low-risk group was significantly better than that of the high-risk group. Independent prognostic analysis showed that the GILncSig could independently predict the prognosis of patients with HCC. In addition, the GILncSig was correlated with the mutation rate of the HCC genome, indicating that it has the potential to measure the degree of genome instability. In GILncSig, LUCAT1 with the highest risk factor was further validated as a risk factor for HCC in vitro. The ESTIMATE analysis showed a significant difference in stromal scores and ESTIMATE scores between the two groups. Multiple immune checkpoints had higher expression levels in the high-risk group. The ssGSEA results showed higher levels of tumor-antagonizing immune cells in the low-risk group compared with the high-risk group. Finally, the GILncSig score was associated with chemotherapeutic drug sensitivity and immunotherapy efficacy of patients with HCC. Conclusion: Our research indicates that GILncSig can be used for prognostic evaluation of patients with HCC and provide new insights for clinical decision-making and potential therapeutic strategies.