Physiological Microenvironment Dependent Self-Cross-Linking of Multifunctional Nanohybrid for Prolonged Antibacterial Therapy via Synergistic Chemodynamic-Photothermal-Biological Processes.

Herein, a multifunctional nanohybrid (PL@HPFTM nanoparticles) was fabricated to perform the integration of chemodynamic therapy, photothermal therapy, and biological therapy over the long term at a designed location for continuous antibacterial applications. The PL@HPFTM nanoparticles consisted of a polydopamine/hemoglobin/Fe2+ nanocomplex with comodification of tetrazole/alkene groups on the surface as well as coloading of antimicrobial peptides and luminol in the core. During therapy, the PL@HPFTM nanoparticles would selectively cross-link to surrounding bacteria via tetrazole/alkene cycloaddition under chemiluminescence produced by the reaction between luminol and overexpressed H2O2 at the infected area. The resulting PL@HPFTM network not only significantly damaged bacteria by Fe2+-catalyzed ROS production, effective photothermal conversion, and sustained release of antimicrobial peptides but dramatically enhanced the retention time of these therapeutic agents for prolonged antibacterial therapy. Both in vitro and in vivo results have shown that our PL@HPFTM nanoparticles have much higher bactericidal efficiency and remarkably longer periods of validity than free antibacterial nanoparticles.

Antifreezing, Antidrying, and Conductive Hydrogels for Electronic Skin Applications at Ultralow Temperatures.

Although conductive hydrogel-based flexible electronic devices have superb flexibility and high conductivities, they tend to malfunction in dry or frigid areas. Herein, an ultralow-temperature tolerant, antidrying, and conductive composite hydrogel is designed for electronic skin applications on the basis of the synergy of double-cross-linked polymer networks, Hofmeister effect, and electrostatic interaction and fabricated by in situ free radical polymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid and acrylic acid in the presence of poly(vinyl alcohol) and conductive MXene sheets, followed by impregnation with LiCl. Thanks to the synergy of LiCl and the charged polar terminal groups of the synthesized polymers, the composite hydrogel can not only bear an ultralow temperature of -80 °C without freezing but also maintain its original mass. Meanwhile, the resultant hydrogel possesses satisfactory self-regeneration ability benefiting from the moisturizing effect of LiCl. The conductive network of MXene sheets greatly improves the ionic conductivity of the hydrogel at low temperatures, exhibiting an ionic conductivity of 1.4 S m-1 at -80 °C. Furthermore, the electronic skin assembled by the multifunctional hydrogel is efficient in monitoring human motions at -80 °C. The antifreezing and antidrying features along with favorable ionic conductivity, high tensile strength, and outstanding flexibility make the composite hydrogel promising for applications in frigid and dry regions.

Cost-effectiveness analysis of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma.

BACKGROUND: To evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system. METHODS: A lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients' lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results. RESULTS: The Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were $26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was $22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than $12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage. CONCLUSION: Under the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.

Recent progress on polymerization-induced emission.

The aggregate luminescence behaviors of polymeric luminescent materials have been attracting great attention. However, the importance of the polymerization process on luminescence, namely, polymerization-induced emission (PIE), has rarely been overviewed. In this review, recent advances in polymerization with PIE effects are summarized, including PIE with aromatic rings based on one-/two-/multi-component polymerizations, and PIE without aromatic rings according to disparate mechanisms of polymerizations. Typical examples are selected to elaborate the basic design principles, as well as the properties and potential applications of the luminous polymers. Moreover, the challenges and perspectives in this area are also discussed.

Acid-base responsive multifunctional poly(formyl sulfide)s through a facile catalyst-free click polymerization of aldehyde-activated internal diynes and dithiols.

Acid-base equilibria play a critical role in biological processes and environmental systems. The development of innovative fluorescent polymeric materials to monitor acid-base equilibria is highly desirable. Herein, a novel catalyst-free click polymerization of aldehyde-activated internal diynes and dithiols was established, and exclusively Markovnikov poly(formyl sulfide)s (PFSs) with high molecular weights and moderate stereoregularity were produced in high yields. Because of the aromatic units and sulfur atoms in their main chains, these polymers possessed high refractive index values. By introducing the fluorene and aldehyde moieties, the resulting PFSs could act as a fluorescent sensor for sensitive hydrazine detection. Taking advantage of the reaction of the aldehyde group and hydrazine, imino-PFSs with remarkable and reversible fluorescence change through alternating fumigation with HCl and NH3 were easily acquired and further applied in multicolor patterning, a rewritable material and quadruple-mode information encryption. Additionally, a test strip of protonated imino-polymer for the tracking of bioamines in situ generated from marine product spoilage was also demonstrated. Collectively, this work not only provides a powerful click polymerization to enrich the multiplicity of sulfur-containing materials, but also opens up enormous opportunities for these functional polysulfides in diverse applications.

Surmounting Cancer Drug Resistance: New Perspective on RNA-Binding Proteins.

RNA-binding proteins (RBPs), being pivotal elements in both physiological and pathological processes, possess the ability to directly impact RNA, thereby exerting a profound influence on cellular life. Furthermore, the dysregulation of RBPs not only induces alterations in the expression levels of genes associated with cancer but also impairs the occurrence of post-transcriptional regulatory mechanisms. Consequently, these circumstances can give rise to aberrations in cellular processes, ultimately resulting in alterations within the proteome. An aberrant proteome can disrupt the equilibrium between oncogenes and tumor suppressor genes, promoting cancer progression. Given their significant role in modulating gene expression and post-transcriptional regulation, directing therapeutic interventions towards RBPs represents a viable strategy for combating drug resistance in cancer treatment. RBPs possess significant potential as diagnostic and prognostic markers for diverse cancer types. Gaining comprehensive insights into the structure and functionality of RBPs, along with delving deeper into the molecular mechanisms underlying RBPs in tumor drug resistance, can enhance cancer treatment strategies and augment the prognostic outcomes for individuals afflicted with cancer.

Efficacy and safety of proton pump inhibitors and H2 receptor antagonists in the initial non­eradication treatment of duodenal ulcer: A network meta­analysis.

The present network meta-analysis aimed to enhance the corresponding evidence with respect to the efficacy and safety of pharmaceuticals treatments. Frequentist network meta-analysis was used. Medical literature up to November 2022 was searched for randomized clinical trials assessing the efficacy and safety of these pharmaceuticals, either compared with each other or compared with placebo. With the exception of ranitidine (300 mg four times daily) and vonoprazan (20 mg once daily) having lower safety than placebo, the efficacy and safety of the remaining treatments were superior to placebo. Cimetidine (400 mg four times daily) and pantoprazole (40 mg once daily) were ranked first in terms of efficacy. The frequentist network meta-analysis shows that for cimetidine (except 400 mg once daily), famotidine, rabeprazole, ilaprazole, lansoprazole (except 7.5 mg once daily) and omeprazole (except 10 mg once daily or 30 mg once daily), the efficacy comparison between the different doses of each of the aforementioned pharmaceuticals did not indicate statistically significant differences. In conclusion, pantoprazole (40 mg once daily) was the best choice for the initial non-eradication treatment of patients with duodenal ulcer, and cimetidine (400 mg twice daily), omeprazole (20 mg once daily), lansoprazole (15 mg once daily), ilaprazole (5 mg once daily) and rabeprazole (10 mg once daily) could be used as the first choice. If the aforementioned pharmaceuticals cannot be prescribed, famotidine (40 mg twice daily) is recommended.

Proteomic investigation and biomarker identification of lung and spleen deficiency syndrome in HIV/AIDS immunological nonresponders.

Background: Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) immunological nonresponders (HIV/AIDS-INRs) whose CD4+ cell counts do not rebound after highly active antiretroviral therapy (HAART) treatment usually experience severely impaired immune function and high mortality. Traditional Chinese medicine (TCM) has many advantages in the field of AIDS, especially its promotion of patients' immune reconstitution. Accurate differentiation of TCM syndromes is a prerequisite for guiding an effective TCM prescription. However, the objective and biological evidence for identification of the TCM syndromes in HIV/AIDS-INRs remains lacking. Lung and spleen deficiency (LSD) syndrome, a typical HIV/AIDS-INR syndrome, was examined on in this study. Methods: We first performed a proteomic study of LSD syndrome in INRs (INRs-LSD) using tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS) and screened them against the healthy and undocumented identifiable groups. The TCM syndrome-specific proteins were subsequently validated based on bioinformatics analysis and enzyme-linked immunosorbent assay (ELISA). Results: A total of 22 differentially expressed proteins (DEPs) were screened in INRs-LSD compared to the healthy group. Based on bioinformatic analysis, these DEPs were found to be mainly associated with the immunoglobin A (IgA)-generated intestinal immune network. In addition, we examined the TCM syndrome-specific proteins alpha-2-macroglobulin (A2M) and human selectin L (SELL) with ELISA and found that they were both upregulated, which was consistent with the proteomic screening results. Conclusions: A2M and SELL were finally identified as potential biomarkers for INRs-LSD, providing a scientific and biological basis for identifying typical TCM syndromes in HIV/AIDS-INRs and an opportunity to build a more effective TCM treatment system for HIV/AIDS-INRs.

Adaptive and Adjustable MXene/Reduced Graphene Oxide Hybrid Aerogel Composites Integrated with Phase-Change Material and Thermochromic Coating for Synchronous Visible/Infrared Camouflages.

Although single-function camouflage under infrared/visible bands has made great advances, it is still difficult for camouflage materials to cope with the synergy detection spanning both visible and infrared spectra and adapt to complex and variable scenarios. Herein, a trilayer composite integrating thermal insulation, heat absorption, solar/electro-thermal conversions, and thermochromism is fabricated for visible and infrared dual camouflages by combining anisotropic MXene/reduced graphene oxide hybrid aerogel with the n-octadecane phase change material in its bottom and a thermochromic coating on its upper surface. Benefiting from the synergetic heat-transfer suppression derived from the thermal insulation of the porous aerogel layer and the heat absorption of the n-octadecane phase-change layer, the composite can serve as a cloak to hide the target signatures from the infrared images of its ambient surroundings during the day in the jungle and at night in all scenes and can assist the target in escaping visual surveillance by virtue of its green appearance. For desert scenarios, the composite can spontaneously increase its surface temperature via its solar-thermal energy conversion, merging infrared images of the targets into the high-temperature surroundings; meanwhile, it can vary the surface color from the original green to yellow, enabling the target to visually disappear from ambient sands and hills. This work provides a promising strategy for designing adaptive and adjustable integrated camouflage materials to counter multiband surveillance in complicated environments.

Starting-up performances and microbial community shifts in the coupling process (SAPD-A) with sulfide autotrophic partial denitrification (SAPD) and anammox treating nitrate and ammonium contained wastewater.

A novel coupling process (SAPD-A) with sulfide autotrophic partial denitrification (SAPD) (NO3--N→NO2--N) and anaerobic ammonium oxidation (Anammox) was developed using anaerobic sequencing batch reactor (ASBR) in this work. The integrated process comprised two stages. Firstly, the starting-up of SAPD process succeeded by gradually increasing the influent nitrate and sulfide in 95 days. The average nitrate removal efficiency (NRE) and NO2--N accumulation rates were 71.24% ± 0.21% and 46.44% ± 0.53% at SAPD process (days 75-95). Then, successful coupling process (SAPD-A) was implemented in two stages (stage I and stage II of SAPD-A). In stage I, it is feasible to promote the successful construction of SAPD-A process by elevating influent ammonium only based on SAPD system, making the NRE increased from 44.45% ± 0.46% (day 95) to 64.62% ± 0.12% at the end of stage I in SAPD-A system (day 126). Meanwhile, the ammonium nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TN-RE) also rose up to 42.46% ± 2.02% and 63.28% ± 0.54% respectively. Furthermore, the average ARE, NRE and TN-RE during the stage II in the bioreactor could reach 65.17% ± 1.45%, 74.50% ± 0.81% and 77.81% ± 0.37% by loading some biofilters (with of approximate 10% of the volume of the bioreactor) attached anaerobic ammonium oxidation bacteria (AnAOB). High-throughput sequencing results showed that the dominant genera concerning nitrogen removal were norank_f_norank_o_Fimbriimonadates (with the abundance of 2.88-8.54%), norank_ o_ norank _ c_ OM190 (2.48-4.41%), norank_f_norank_o_norank_c_WWE3 (11.01-17.69%), subgroup_10 (1.97-3.81%), Limnobacter（2.17-3.49%）, norank_f_n orank_ o_norank_ c_OLB14 (2.03-5.23%), norank-f-PHOS-HE36 (2.18-5.5%), Ellin6067 (1.34-2.24%) and Candidatus_ Brocadia (1.95-2.42%) during the whole starting-up period of coupling SAPD-A process. Batch experiments revealed that the sulfide was fully oxidized within 2 h, with the maximum reaction rate of 38.30 ± 1.53 mg (L h)-1 in the first 1 h. Simultaneously, the concentration of nitrate sharply decreased from 53.08 ± 0.23 mg L-1 to 24.16 ± 0.42 mg L-1 with the reaction rate of 66.41 ± 2.12 mg (L h)-1 in 0.5 h. Also, the ammonium concentration significantly declined from 47.88 ± 0.34 mg L-1 to 10.98 ± 0.39 mg L-1 in 8 h. Anammox process was responsible for the dominant nitrogen removal in the coupling SAPD-A system.

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.

Fabrication and Mechanical Properties of High-Durability Polypropylene Composites via Reutilization of SiO2 In-Situ-Synthesized Waste Printed Circuit Board Powder.

This paper focuses on the characterization of the physico-chemical properties, surface modification, residual copper content and in situ hybrid inorganic particle modification of polypropylene (PP) composites reinforced by waste printed circuit board powder (WPCBP). A series of WPCBP/SiO2 hybrids (TSW) were prepared by a sol-gel method at different pH values. Characterization results revealed the in situ generation of SiO2 on the surface of WPCBP, and showed that with an increase in pH value, the size of SiO2 particles increased gradually and the copper content decreased in the TSW powder. The mechanical properties, oxidation induction time (OIT) and thermal properties of PP composites were improved by reinforcement with TSW, which might be ascribed to the formation of serrated interfaces. This work not only develops a powerful method to enhance the properties of PP/WPCBP composites, but also provides an environmentally sustainable approach to the high-added-value reutilization of WPCBP.

Aggregation-Induced Emission Luminogen-Based Dual-Mode Enzyme-Linked Immunosorbent Assay for Ultrasensitive Detection of Cancer Biomarkers in a Broad Concentration Range.

The enzyme-linked immunosorbent assay (ELISA) is one of the most commonly used methods for measuring antibodies and antigens in biological samples. However, developing new ELISAs with high detection sensitivity and broad detection dynamic ranges without resorting to complicated signal processing and equipment setups remains a challenge. In this work, we report a strategy to simultaneously improve the detection sensitivity and broaden the dynamic range by replacing the chromogenic reagents used in traditional ELISAs with an aggregation-induced emission luminogen (AIEgen). The developed AIE-ELISA could generate complementary absorbance and fluorescence signals with a linear detection range of 1.6-25,000 pg/mL. The application of this dual-mode AIE-ELISA in the detection of the prostate-specific antigen (PSA) realized a limit of detection of 1.3 pg/mL (3.78 × 10-14 M) and dynamic range improvement of approximately 2 orders of magnitude compared to a single-mode ELISA, which enabled it to discriminate a minor PSA difference in a patient's serum. The simpler experimental operation, faster enzyme response speed, and better photostability of AIEgen than the traditional chromogenic reagents used in ELISAs showed that our developed AIE-ELISA holds great potential in the fields of immunoassay, immunohistochemistry, and immunocytochemistry.

PARP1 Is Targeted by miR-519a-3p and Promotes the Migration, Invasion, and Tube Formation of Ovarian Cancer Cells.

Background: Poly ADP-ribose polymerase 1 (PARP1) has been discovered to be implicated in ovarian cancer (OC), but its interaction with microRNA (miR)-519a-3p remained poorly understood. This study aimed to uncover their roles and interactions in OC. Materials and Methods: Clinical tissue from OC patients and adjacent normal tissue were collected, and the survival rates of OC patients with high or low PARP1 expression were analyzed by Kaplan-Meier curve. After transfection, OC cell viability, migration, and tube formation were detected with cell counting kit-8 (CCK-8) assay, scratch assay, and tube formation assay, respectively. The target gene of miR-519a-3p and potential binding sites between them were predicted with TargetScan and confirmed using a dual-luciferase reporter assay. Relative expressions of miR-519a-3p, PARP1, E-cadherin, N-cadherin, SNAIL, vascular endothelial growth factor (VEGF), and p53 were measured by quantitative real-time polymerase chain reaction and Western blot as needed. Results: PARP1 expression was upregulated in OC, which was related to poor prognosis of OC patients. Silencing PARP1 decreased PARP1 expression and suppressed viability, migration, invasion, and tube formation in OC cells, while overexpressed PARP1 did the opposite. PARP1 was the target gene of miR-519a-3p, and it reversed the effects of miR-519a-3p on the migration, invasion, and tube formation of OC cells by upregulating the expressions of PAR, PARP1, N-cadherin, SNAIL, and VEGF and downregulating those of E-cadherin and p53. Conclusion: PARP1, a target gene of miR-519a-3p, promoted the migration, invasion, and tube formation of OC cells, providing a possible therapeutic target for treatment of OC patients.

Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation.

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid-activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate-induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.

Comparative serum microRNA array analysis of the spleen-stomach dampness-heat syndrome in different diseases: Chronic hepatitis B and chronic gastritis.

Spleen-stomach dampness-heat syndrome (SSDHS) is the common Traditional Chinese Medicine (TCM) syndrome observed in both chronic hepatitis B (CHB) and chronic gastritis (CG). The specialized TCM prescription for CHB and CG patients with SSDHS is same, but there is limited information about the biological characteristics of this TCM syndrome. This study aimed to identify the serum miRNAs profile for the SSDHS in two different diseases in order to evaluate the miRNA-mediated biological characteristics of this TCM syndrome. We performed comparative microarray analysis of serum miRNA expression profiles in 10 CHB patients with SSDHS (SSDHS-CHB), 10 CG patients with SSDHS (SSDHS-CG), and 10 healthy controls (HC). The selected miRNAs were further validated by qRT-PCR in 13 SSDHS-CHB patients, 13 SSDHS-CG patients, and 13 HC. Moreover, bioinformatics analysis (GO and KEGG pathway enrichment analyses) was applied to identify the involved target genes and pathways for these selected miRNAs. Nine significantly differentially expressed (SDE)-miRNAs in the SSDHS-CHB group and 24 SDE-miRNAs in the SSDHS-CG group were identified, compared with the HC group (fold change >2.0 and p < .05). Among these, upregulated hsa-miR-483-3p and downregulated hsa-miR-223-3p were identified as the common SDE-miRNAs for both SSDHS-CHB and SSDHS-CG groups. Bioinformatics analysis of the common SDE-miRNA's target genes showed their involvement in the regulation of inflammation, immune response, and tumorigenesis. SSDHS-specific hsa-miR-483-3p and hsa-miR-223-3p identified in this study indicated a relevance to the underlying biological basis of SSDHS, and may provide scientific basis for the application of same TCM prescription in CHB and CG.

Study on the Expression Differences and the Correlation with H2BE Gene of Th Related Cytokines in SSDHS and LDSDS TCM-Syndromes of CHB Patients.

Although our previous studies revealed that H2BE exhibited significantly differential expression between two CHB TCM-syndromes: Spleen-stomach dampness-heat syndrome, SSDHS and liver-depression spleen-deficiency syndrome, LDSDS, the underlying mechanisms remain largely unknown. Recent studies showed that dynamic expression fluctuation of Th related cytokines in CHB TCM-syndromes, and furthermore, their expression levels were largely regulated by H2BE. This study aims to detect the expression level differences of Th related cytokines between these two TCM-syndromes and further investigate the underlying regulatory mechanisms. The expression levels of the four Th related cytokines and H2BE were analyzed and the protein-protein interaction networks between H2BE and the four cytokines were constructed. Our results suggested that almost all the cytokines were significantly upregulated compared with the healthy group (P < 0.05). Interestingly, among the four cytokines, only IL-4 and INF-γ showed statistical significance between these two syndromes. The protein-protein interaction networks demonstrated that H2BE was indirectly associated with IL-4 and IL-10, and H2BE may regulate the expression levels of cytokines through GATA3. Taken together, our results indicated that IL-4 and INF-γ are two representative cytokines that may serve as two potential biochemical indicators of SSDHS and LDSDS in CHB patients; except what has been reported, our study found that one possible way for H2BE to regulate the expression of cytokines is to interact with GATA3 directly or indirectly.

Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study.

BACKGROUND: Hyperandrogenism (HA), inflammation, and oxidative damage play key roles in the pathophysiology of polycystic ovary syndrome (PCOS). Whether vitamin D adjuvant therapy improves hormonal, inflammation, and oxidative damage in PCOS patients has aroused widespread interest, but the results are controversial. To evaluate the effect of vitamin D supplementation on hormonal, oxidative stress, and inflammatory parameters in patients with PCOS. METHODS: A literature search was conducted in Medline, the Cochrane Library, EMBASE, and Web of Science for studies related to PCOS and vitamin D supplementation. All reports of randomized controlled trials (RCTs) published before December 2019 were identified. The fixed-effects model or random-effects model was used to calculate pooled estimates of standardized differences in means (SMD) with 95% confidence intervals (CI). RESULTS: A total of 956 identified studies were retrieved, and eighteen RCTs involving 1,060 participants were ultimately included in the current meta-analysis. The pooled results demonstrated that vitamin D supplementation in patients with PCOS resulted in a significant improvement in serum total testosterone (TT), high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and malondialdehyde (MDA). No significant effect on free testosterone (FT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), free androgen index (FAI), nitric oxide (NO), and total glutathione (GSH) levels was found. Subgroup analysis showed that vitamin D supplementation reduced hs-CRP and MDA irrespective of the treatment course, type of vitamin D intervention, supplementation frequency, and dosage. Twelve weeks of vitamin D supplementation improved TT and TAC while low-dose vitamin D supplementation (≤1,000 IU/day) improved TT and DHEA-S. Vitamin D co-supplementation reduced TT, FT, and DHEA-S, while a daily supplementation regime improved TT, DHEA-S, and TAC in patients with PCOS. CONCLUSIONS: The current meta-analysis demonstrates that vitamin D supplementation in patients with PCOS resulted in an improvement in the levels of TT, hs-CRP, TAC, and MDA, but did not affect FT, DHEA-S, SHBG, FAI, NO, and GSH levels. Vitamin D co-supplementation, low-dose vitamin D supplementation (≤1,000 IU/day), and daily supplementation frequency appeared to be more conducive to improving hormones, inflammation, and oxidative stress in PCOS patients.

The role of the retinoid receptor, RAR/RXR heterodimer, in liver physiology.

Activated by retinoids, metabolites of vitamin A, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) play important roles in a wide variety of biological processes, including embryo development, homeostasis, cell proliferation, differentiation and death. In this review, we summarized the functional roles of nuclear receptor RAR/RXR heterodimers in liver physiology. Specifically, RAR/RXR modulate the synthesis and metabolism of lipids and bile acids in hepatocytes, regulate cholesterol transport in macrophages, and repress fibrogenesis in hepatic stellate cells. We have also listed the specific genes that carry these functions and how RAR/RXR regulate their expression in liver cells, providing a mechanistic view of their roles in liver physiology. Meanwhile, we pointed out many questions regarding the detailed signaling of RAR/RXR in regulating the expression of liver genes, and hope future studies will address these issues.

Biological differentiation of traditional Chinese medicine from excessive to deficient syndromes in AIDS: Comparative microRNA microarray profiling and syndrome-specific biomarker identification.

Traditional Chinese medicine (TCM) has been widely applied as a supplementary therapy of human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) in China. TCM has a positive effect on improving the quality of life, prolonging life, and ameliorating the symptoms of HIV/AIDS patients. Yang deficiency of spleen and kidney (YDSK) syndrome is a typical deficient TCM syndrome in AIDS patients, and accumulation of heat-toxicity (AHT) syndrome is a common excessive syndrome in the earlier stage of AIDS. Thus, accurate diagnosis of these two syndromes can improve the targeted treatment effect, and predict the prognosis of the disease. However, the scientific basis of TCM syndromes remains lacking, greatly hindering the accuracy of diagnosis and effectiveness of treatment. In this research, microRNA (miRNA) microarray and quantitative real-time polymerase chain reaction combined with bioinformatics were used for comparative analysis between YDSK and AHT patients. Significantly differential expressed miRNAs (SDE-miRNAs) of each TCM syndrome were identified, including hsa-miR-766-3p and hsa-miR-1260a and so on, as well hsa-miR-6124, hsa-let-7g-5p and so on, for YDSK and AHT, respectively. Biological differences were found between their SDE-miRNAs based on bioinformatics analyses, for example, ErbB signaling pathway mainly linked to AHT, while focal adhesion dominated in YDSK. Syndrome-specific SDE-miRNAs were further identified as potential biomarkers, including hsa-miR-30e-5p, hsa-miR-144-5p for YDSK and hsa-let-7g-5p, hsa-miR-126-3p for AHT, respectively. All of them have laid biological and clinical bases for TCM diagnosis and treatment of AIDS syndrome at the miRNA level, offering potential diagnostic indicators of immune reconstitution.