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.

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.

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.

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.

Epidemiology-based analysis of the risks and elimination strategies of the monkeypox outbreak in 2022.

Human monkeypox, caused by monkeypox virus, has spread unprecedentedly to more than 100 countries since May 2022. Here we summarized the epidemiology of monkeypox through a literature review and elucidated the risks and elimination strategies of this outbreak mainly based on the summarized epidemiology. We demonstrated that monkeypox virus became more contagious and less virulent in 2022, which could result from the fact that the virus entered a special transmission network favoring close contacts (i.e., sexual behaviors of men who have sex with men outside Africa) and the possibility that the virus accumulated a few adaptive mutations. We gave the reasons to investigate whether cattle, goats, sheep, and pigs are susceptible to monkeypox virus and whether infection with monkeypox virus could be latent in some primates. We listed six potential scenarios for the future of the outbreak (e.g., the outbreak could lead to endemicity outside Africa with increased transmissibility or virulence). We also listed multiple factors aiding or impeding the elimination of the outbreak. We showed that the control measures strengthened worldwide after the World Health Organization declared the outbreak a public health emergency of international concern (PHEIC) could eliminate the outbreak in 2022. We clarified eight strategies, i.e., publicity and education, case isolation, vaccine stockpiling, risk-based vaccination or ring vaccination, importation quarantine, international collaboration, and laboratory management, for the elimination of the outbreak.

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.

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.

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.

Partial reprogramming strategy for intervertebral disc rejuvenation by activating energy switch.

Rejuvenation of nucleus pulposus cells (NPCs) in degenerative discs can reverse intervertebral disc degeneration (IDD). Partial reprogramming is used to rejuvenate aging cells and ameliorate progression of aging tissue to avoiding formation of tumors by classical reprogramming. Understanding the effects and potential mechanisms of partial reprogramming in degenerative discs provides insights for development of new therapies for IDD treatment. The findings of the present study show that partial reprogramming through short-term cyclic expression of Oct-3/4, Sox2, Klf4, and c-Myc (OSKM) inhibits progression of IDD, and significantly reduces senescence related phenotypes in aging NPCs. Mechanistically, short-term induction of OSKM in aging NPCs activates energy metabolism as a "energy switch" by upregulating expression of Hexokinase 2 (HK2) ultimately promoting redistribution of cytoskeleton and restoring the aging state in aging NPCs. These findings indicate that partial reprogramming through short-term induction of OSKM has high therapeutic potential in the treatment of IDD.

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.

How useful is sentinel lymph node biopsy for the status of lymph node metastasis in cT1N0M0 gastric cancer? A systematic review and meta-analysis.

Sentinel lymph node biopsy (SLNB) is intriguing because it is expected to further expand the indication of endoscopic resection (ER) for cT1N0M0 gastric cancer and as an additional operation for post-ER gastric cancer. The aim of our study was to perform a systematic review and meta-analysis on the feasibility and diagnostic value of SLNB technique in patients with cT1N0M0 gastric cancer. Eligible studies were systematically searched in PubMed, Embase, and Cochrane Library databases from inception to April 2020. A random-effect model was used to pool the data, and subgroup analysis was used to explain the heterogeneities. A total of 22 clinical studies (1993 patients with cT1N0M0 gastric cancer) were included. The pooled SLN identification rate, sensitivity, specificity, and diagnostic odds ratio with 95% confidence intervals were 0.99 (0.99-1.00), 0.92 (0.88-0.95), 1.00 (1.00-1.00), and 832.8 (395.5-1753.6), respectively. The summary receiver operator characteristic displayed a test accuracy of 99.3%. Subgroup analysis found an improved SLN sensitivity for studies with the mean number of SLNs > 4 and studies stained with a combination of hematoxylin-eosin with immunohistochemistry (HE + IHC). Further, studies using the basin dissection were associated with a higher SLN identification rate. The current meta-analysis provides data that favors the use of SLNB for predicting the status of lymph node metastasis in patients with cT1N0M0 gastric cancer. However, establishing standard procedure and suitable criteria for further application and optimization of SLNB is urgently needed.

Molecular-level variation of dissolved organic matter and microbial structure of produced water during its early storage in Fuling shale gas field, China.

Shale gas-produced water (PW), the waste fluid generated during gas production, contains a large number of organic contaminants and high salinity matrix. Previous studies generally focused on the end-of-pipe treatment of the PW and ignored the early collection process. In this study, the transformation of the molecular composition and microbial community structure of the PW in the transportation and storage process (i.e., from the gas-liquid separator to the storage tank) were investigated. As the PW was transported from the gas-liquid separator to the portable storage tank, the dissolved organic matter (DOM) showed greater saturation, less oxidation, and lower polarity. DOMs with high O/C and low H/C ratios (numbers of oxygen and hydrogen divided by numbers of carbon) were eliminated, which may be due to precipitation or adsorption by the solids suspended in the PW. The values of double-bond equivalent (DBE), DBE/C (DBE divided by the number of carbon), and aromatic index (AI) decreased, likely because of the microbial degradation of aromatic compounds. The PW in the gas-liquid separator presented a lower biodiversity than that in the storage tank. The microbial community in the storage tank showed the coexistence of anaerobes and aerobes. Genera related to biocorrosion and souring were detected in the two facilities, thus indicating the necessity of more efficient anticorrosion strategies. This study helps to enhance the understanding of the environmental behavior of PW during shale gas collection and provides a scientific reference for the design and formulation of efficient transportation and storage strategies to prevent and control the environmental risk of shale gas-derived PW.

Neuroprotective effects of Camellia nitidissima Chi leaf extract in hydrogen peroxide-treated human neuroblastoma cells and its molecule mechanisms.

Camellia nitidissima Chi (CNC) is a famous medicinal and edible plant with the name of "Tea for Longevity" in Guangxi province of China. In present study, we determined the protective effect of extract from CNC leaves on H2O2-induced cell injury and its underlying mechanisms in human neuroblastoma (SH-SY5Y) cells. The ethyl acetate fraction of CNC leaves (CLE, 50-200 µg/ml) treatment significantly increased the cell viability of H2O2-treated SH-SY5Y cells and reduced the leakage of LDH in a reversed "U"-shape manner. It was confirmed by Hoechst 33,342 staining that CLE attenuated H2O2-induced apoptosis in SH-SY5Y cells. The CLE (100 and 150 µg/ml) treatment significantly relieved H2O2-induced oxidative stress by decreasing intracellular ROS level, and increasing the activities of superoxide dismutase (SOD) and catalase (CAT). Western blot analysis demonstrated that the CLE treatment reserved H2O2-induced decrease of pCREB (Ser133) expression, and its downstream protein BDNF. In addition, 37 phenolic compounds in CLE were identified by UPLC-TOF MS/MS, and the main active phytochemicals seemed to be catechins, quercetin, kaempferol, and their derivatives. In conclusion, the data analysis showed that the neuroprotective effect of CNC leaves might be achieved via synergistically boosting endogenous antioxidant defenses and neurotrophic signaling pathway. These results suggest that CNC leaves are valuable resources for functional foods and beverages.

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.