Enantiopure trigonal bipyramidal coordination cages templated by in situ self-organized D2h-symmetric anions.

The control of a molecule's geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D3-symmetric trigonal bipyramidal coordination cages. Specifically, D2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.

The potential of indocyanine green fluorescence detection in surgical cut margin of breast conserving surgery.

Background: Fluorescence-guided surgery (FGS) is a cutting-edge technology that uses near-infrared (NIR) fluorescence imaging to guide surgeons in surgery. Indocyanine green (ICG) is a fluorescent dye, which can be used for in vivo imaging of tumor cells. We aimed to explore the use of ICG fluorescence-guided technology as a rapid intraoperative margin assessment method for breast cancer surgery. In addition, we also compared the dose selection of ICG. Methods: This was a non-randomized prospective cohort study. Data were collected between August 2021 and October 2022 in the Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University. Upon specimen removal, tumor margins were immediately analyzed by ICG fluorescence detection and then sent to the pathology department for intraoperative frozen section analysis and subsequent routine pathological examination. Abnormal margin rates were calculated and compared using intraoperative frozen section analysis and under the guidance of ICG fluorescence. Results: The study included 69 cases of breast cancer patients who underwent tumor resection assisted by ICG fluorescence-guided technology, including 18 patients with a 0.5 mg/kg dose and 51 patients with a 1.0 mg/kg dose. According to the study findings, the ICG test achieved a sensitivity of 81.82% and a specificity of 75.82%. At a dose of 0.5 mg/kg, the sensitivity was 66.67% whereas the specificity was 93.33%. At the dose of 1 mg/kg, the sensitivity was 87.5%, and the specificity was 74.42%. Similarly, for intraoperative frozen section analysis, the sensitivity was 81.82%, but the specificity was enhanced to 94.83%. Positive surgical cut margin was not identified in 2/69 by ICG fluorescence and frozen section analysis respectively. Conclusions: The sensitivity of ICG fluorescence detection is comparable to that of frozen section analysis, but the specificity is poor. The sensitivity increased and the specificity decreased at 1 mg/kg compared to the 0.5 mg/kg dose. ICG fluorescence can be used as a supplementary tool for frozen section analysis. These findings support further development and clinical performance assessment of ICG fluorescence.

Four three-dimensional rare earth metal - organic framework fluorescent sensor for efficient detection of gentamicin sulfate and Fe3.

Excessive use of gentamicin sulfate can cause severe nephrotoxicity and ototoxicity, abnormal levels of Fe3+ intake can also cause serious damage to body. Therefore, establishing a fast and accurate detection method for the above-mentioned substances is of great significance. However, traditional detection methods such as high-performance liquid chromatography still have certain problems such as high cost and complex operation. Fluorescent MOFs are favored by analysts due to their high specific surface area, high porosity, adjustable pore size, and good stability. In this paper, we have synthesized four rare earth MOFs based on the pyridinecarboxylic acid ligand (H2L), which are [Eu(L)1/2H2O]n, [Gd(L)1/2H2O]n, [Sm(L)1/2H2O]n, [Y(L)3/2H2O·DMF]n. The structures of four MOFs were confirmed by single crystal X-ray diffraction, which proved that MOF-1, MOF-2 and MOF-3 were isostructural, and all the four MOFs were three-dimensional structures. In the fluorescence test, gentamicin sulfate and Fe3+ can cause significant fluorescence quenching of MOF-1 and MOF-4 respectively, and show good selectivity and anti-interference performance, as well as low detection limit and wide detection range. This work may provide a possibility for the detection of gentamicin sulfate and iron ions in complex environments.

Polyacrylonitrile Based Triblock Copolymer Binder Enabling Excellent Performance toward LiNi0.5Mn1.5O4 and Sulfur Based Batteries.

There is an urgent need for lithium-ion batteries with high energy density to meet the increasing demand for advanced devices and ecofriendly electric vehicles. Spinel LiNi0.5Mn1.5O4 (LNMO) is the most promising cathode material for achieving high energy density due to its high operating voltage (4.75 V vs Li/Li+) and impressive capacity of 147 mAh g-1. However, the binders conventionally used are prone to high potential and oxidation at the cathode side, resulting in a loss of the ability to bond active material and conductive agent integrity. This can lead to severe capacity fading and irreversible battery failure. This study demonstrates that incorporating acrylic anhydride and methyl methacrylate into conventional acrylonitrile through solution polymerization improves the binding energy and voltage resistance. The results indicate that the triblock poly(acrylonitrile-methyl methacrylate-acrylic anhydride) (PAMA) binder has a much higher peeling strength (0.506 N cm-1) compared to its polyvinylidene fluoride (PVDF) counterpart (0.3 N cm-1), making it a more feasible strategy. When assembled with LiNi0.5Mn1.5O4, the PAMA based electrode maintains a capacity retention of 70.7% after 800 cycles at 0.1 C, which is significantly higher than the 33.9% retention of the PVDFbased electrode. This is due to the large number of polar groups, including ─C≡N and ─C═O, on PAMA, which are conducive to adsorbing lithium polysulfide. The S@PAMA electrode is tested and maintained a capacity value of 628.7 mAh g-1 after long-term cycling, confirming its ability to effectively suppress the shuttle effect.

Noninvasive microvascular imaging in newborn rats using high-frequency ultrafast ultrasound.

Ultrasound imaging stands as the predominant modality for neonatal health assessment, with recent advancements in ultrafast Doppler (µDoppler) technology offering significant promise in fields such as neonatal brain imaging. Combining µDoppler with high-frequency ultrasound (HF-µDoppler) presents a potential efficient avenue to enhance in vivo microvascular imaging in small animals, notably newborn rats, a crucial preclinical animal model for neonatal disease and development research. It is necessary to verify the imaging performance of HF-µDoppler in preclinical trials. This study investigates the microvascular imaging capabilities of HF-µDoppler using a 30 MHz high-frequency linear array probe in newborn rats. Results demonstrate the clarity of cerebral microvascular imaging in rats aged 1 to 7 postnatal days, extending to whole-body microvascular imaging, encompassing the central nervous system, including the brain and spinal cord. In conclusion, HF-µDoppler technology emerges as a reliable imaging tool, offering a new perspective for preclinical investigations into neonatal diseases and development.

"Rigid-Flexible" Dual-Ferrocene Chimeric Nanonetwork for Simultaneous Tumor-Targeted Tracing and Photothermal/Photodynamic Therapy.

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

Apolipoprotein L3 inhibits breast cancer proliferation and modulates cell cycle via the P53 pathway.

Background: Breast cancer is the second most common cause of cancer-related mortality globally. Apolipoprotein L3 (APOL3), a member of the apolipoprotein family, has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, the functions and underlying mechanisms of APOL3 in breast cancer have yet to be elucidated. Methods: The patient data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) assays were used to assess expression of APOL3. Cell proliferation rates were determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used to examine cell cycle distribution. Western blotting was conducted to investigate the expression of cell cycle related proteins. A xenograft model was used to evaluate the effect of APOL3 in vivo. APOL3-binding proteins were identified through mass spectrometry, co-immunoprecipitation (CO-IP) assay and immunofluorescence assay. Results: APOL3 expression was significantly downregulated in breast cancer, and its low expression was correlated with poor prognostic outcomes. Overexpression of APOL3 suppressed breast cancer cell proliferation, induced cell cycle disruption. Conversely, knockdown of APOL3 promoted cell proliferation. In vivo animal experiments demonstrated that APOL3 overexpression can inhibit tumor proliferation. Mass spectrometry, CO-IP and immunofluorescence assay confirmed the interaction between APOL3 and Y-box binding protein 1 (YBX1). Furthermore, YBX1 knockdown following APOL3 knockdown mitigated the enhanced proliferation. These results provide new ideas for clinically targeting APOL3 to inhibit proliferation in breast cancer. Conclusions: Our findings indicate that APOL3 inhibits breast cancer cell proliferation and cell cycle modulating P53 pathway through the interaction of YBX1.

Constructing drain surrounded double gate structure in AlGaN/GaN HEMT for boosting breakdown voltage.

AlGaN/GaN high electron mobility transistors (HEMTs) play an important role in the field of high-voltage and high-frequency power devices. However, the current collapse effect of the HEMTs under high voltage greatly limits the development of AlGaN/GaN HEMTs. In this work, a breakdown performance enhanced drain surrounded double gate (DSDG) AlGaN/GaN HEMT is investigated. This structure has two separate gates located on the right and the left of the drain. The optimized off-state characteristics are analyzed by the Sentaurus TCAD simulation tool. The additional gate contributes to restraining the movement of electrons injected by the source therefore reducing the source-to-drain punch-through current. Moreover, the energy band pulled up by the relatively low voltage of the right gate helps to alleviate the drain induced barrier lower (DIBL) effect. As a result, DSDG-HEMT could postpone the breakdown by approximately 100 V through suppressing buffer leakage.

HES6 Mediates Oxidative Phosphorylation Pathway to Promote Immune Infiltration of CD8+ T Cells in Lung Adenocarcinoma.

Tumor immunotherapy has recently gained popularity as a cancer treatment strategy. The molecular mechanism controlling immune infiltration in lung adenocarcinoma (LUAD) cells, however, is not well characterized. Investigating the immune infiltration modulation mechanism in LUAD is crucial. LUAD patient samples were collected, and HES6 expression and immune infiltration level of CD8+ T cells in patient tissues were analyzed. Bioinformatics was utilized to identify binding relationship between E2F1 and HES6, and enrichment pathway of HES6. The binding of E2F1 to HES6 was verified using dual-luciferase and ChIP experiments. HES6 and E2F1 expression in LUAD cells was detected. LUAD cells were co-cultured with CD8+ T cells, and the CD8+ T cell killing level, IFN-γ secretion, and CD8+ T-cell chemotaxis level were measured. Expression of key genes involved in oxidative phosphorylation was detected, and the oxygen consumption rate of LUAD cells was assessed. A mouse model was constructed to assay Ki67 expression and apoptosis in tumor tissue. High expression of HES6 promoted CD8+ T-cell infiltration and enhanced T-cell killing ability through oxidative phosphorylation. Further bioinformatics analysis, molecular experiments, and cell experiments verified that E2F1 negatively regulated HES6 by oxidative phosphorylation, which suppressed CD8+ T-cell immune infiltration. In addition, in vivo assays illustrated that silencing HES6 repressed tumor cell immune evasion. E2F1 inhibited HES6 transcription, thereby mediating oxidative phosphorylation to suppress immune infiltration of CD8+ T cells in LUAD. The biological functions and signaling pathways of these genes were analyzed, which may help to understand the possible mechanisms regulating immune infiltration in LUAD.

Odor Fingerprinting of Chitosan and Source Identification of Commercial Chitosan: HS-GC-IMS, Multivariate Statistical Analysis, and Tracing Path Study.

Chitosan samples were prepared from the shells of marine animals (crab and shrimp) and the cell walls of fungi (agaricus bisporus and aspergillus niger). Fourier-transform infrared spectroscopy (FT-IR) was used to detect their molecular structures, while headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was employed to analyze their odor composition. A total of 220 volatile organic compounds (VOCs), including esters, ketones, aldehydes, etc., were identified as the odor fingerprinting components of chitosan for the first time. A principal component analysis (PCA) revealed that chitosan could be effectively identified and classified based on its characteristic VOCs. The sum of the first three principal components explained 87% of the total variance in original information. An orthogonal partial least squares discrimination analysis (OPLS-DA) model was established for tracing and source identification purposes, demonstrating excellent performance with fitting indices R2X = 0.866, R2Y = 0.996, Q2 = 0.989 for independent variable fitting and model prediction accuracy, respectively. By utilizing OPLS-DA modeling along with a heatmap-based tracing path study, it was found that 29 VOCs significantly contributed to marine chitosan at a significance level of VIP > 1.00 (p < 0.05), whereas another set of 20 VOCs specifically associated with fungi chitosan exhibited notable contributions to its odor profile. These findings present a novel method for identifying commercial chitosan sources, which can be applied to ensure biological safety in practical applications.

Strain-Triggered Distinct Oxygen Evolution Reaction Pathway in Two-Dimensional Metastable Phase IrO2 via CeO2 Loading.

A strain engineering strategy is crucial for designing a high-performance catalyst. However, how to control the strain in metastable phase two-dimensional (2D) materials is technically challenging due to their nanoscale sizes. Here, we report that cerium dioxide (CeO2) is an ideal loading material for tuning the in-plane strain in 2D metastable 1T-phase IrO2 (1T-IrO2) via an in situ growth method. Surprisingly, 5% CeO2 loaded 1T-IrO2 with 8% compressive strain achieves an overpotential of 194 mV at 10 mA cm-2 in a three-electrode system. It also retained a high current density of 900 mA cm-2 at a cell voltage of 1.8 V for a 400 h stability test in the proton-exchange membrane device. More importantly, the Fourier transform infrared measurements and density functional theory calculation reveal that the CeO2 induced strained 1T-IrO2 directly undergo the *O-*O radical coupling mechanism for O2 generation, totally different from the traditional adsorbate evolution mechanism in pure 1T-IrO2. These findings illustrate the important role of strain engineering in paving up an optimal catalytic pathway in order to achieve robust electrochemical performance.

Dandelion-like VSe2-embellished CuSe-Co3Se4 hollow nanotube clusters as bifunctional catalysts for high-performance alkaline hydrogen evolution and solar cells.

Among the various non-precious metal catalysts that drive hydrogen evolution reactions (HERs) and dye-sensitized solar cells (DSSCs), transition metal selenides (TMSs) stand out due to their unique electronic properties and tunable morphology. Herein, the multicomponent selenide CuSe-Co3Se4@VSe2 was successfully synthesized by doping with metal element vanadium and selenization on the copper-cobalt carbonate hydroxide (CuCo-CH) template. CuSe-Co3Se4@VSe2 exhibited the dandelion-like cluster structure composed of hollow nanotubes doped with VSe2 nanoparticles. Due to the unique structure and the synergistic effect of various elements, CuSe-Co3Se4@VSe2 showed excellent alkaline HER and DSSC performances. The DSSC based on CuSe-Co3Se4@VSe2 exhibited an impressive power conversion efficiency (PCE) of 9.64 %, which was much higher than that of Pt (8.39 %). Besides, it possessed a low HER overpotential of 76 mV@10 mA cm-2 and a small Tafel slope of 88.9 mV dec-1 in 1.0 M KOH.

Transformation of antibiotics to non-toxic and non-bactericidal products by laccases ensure the safety of Stropharia rugosoannulata.

The substantial use of antibiotics contributes to the spread and evolution of antibiotic resistance, posing potential risks to food production systems, including mushroom production. In this study, the potential risk of antibiotics to Stropharia rugosoannulata, the third most productive straw-rotting mushroom in China, was assessed, and the underlying mechanisms were investigated. Tetracycline exposure at environmentally relevant concentrations (<500 µg/L) did not influence the growth of S. rugosoannulata mycelia, while high concentrations of tetracycline (>500 mg/L) slightly inhibited its growth. Biodegradation was identified as the main antibiotic removal mechanism in S. rugosoannulata, with a degradation rate reaching 98.31 % at 200 mg/L tetracycline. High antibiotic removal efficiency was observed with secreted proteins of S. rugosoannulata, showing removal efficiency in the order of tetracyclines > sulfadiazines > quinolones. Antibiotic degradation products lost the ability to inhibit the growth of Escherichia coli, and tetracycline degradation products could not confer a growth advantage to antibiotic-resistant strains. Two laccases, SrLAC1 and SrLAC9, responsible for antibiotic degradation were identified based on proteomic analysis. Eleven antibiotics from tetracyclines, sulfonamides, and quinolones families could be transformed by these two laccases with degradation rates of 95.54-99.95 %, 54.43-100 %, and 5.68-57.12 %, respectively. The biosafety of the antibiotic degradation products was evaluated using the Toxicity Estimation Software Tool (TEST), revealing a decreased toxicity or no toxic effect. None of the S. rugosoannulata fruiting bodies from seven provinces in China contained detectable antibiotic-resistance genes (ARGs). This study demonstrated that S. rugosoannulata can degrade antibiotics into non-toxic and non-bactericidal products that do not accelerate the spread of antibiotic resistance, ensuring the safety of S. rugosoannulata production.

Time trends in Alzheimer's disease mortality attributable to metabolic risks and smoking in China from 1990 to 2019: an age-period-cohort analysis.

Background: With the increase in the aging population worldwide, Alzheimer's disease has become a rapidly increasing public health concern. In the Global Burden of Disease Study 2019, there are three risk factors judged to have evidence for a causal link to Alzheimer's disease and other dementias: smoking, high body-mass index (HBMI), and high fasting plasma glucose (HFPG). Objective: This study aimed to analyze trends in AD mortality and the relevant burden across China from 1990 to 2019, as well as their correlation with age, period, and birth cohort. Methods: The data were extracted from the GBD 2019. Trends in AD mortality attributable to metabolic risks (HFPG and HBMI) and smoking were analyzed using Joinpoint regression. The age-period-cohort (APC) model was used to evaluate cohort and period effects. Results: From 1990 to 2019, the overall age-standardized mortality rate of AD increased, especially in women. There was an increase in AD mortality due to smoking in the net drift, and it was more significant in women (0.46, 95%CI = [0.09, 0.82]) than men (-0.03, 95%CI = [-0.11, 0.05]). For the cause of HFPG, the net drift values for men and women were 0.82% and 0.43%. For HBMI, the values were 3.14% and 2.76%, respectively, reflecting substantial increases in AD mortality. Conclusion: Time trends in AD mortality caused by metabolic risks and smoking in China from 1990 to 2019 have consistently increased. Therefore, it is necessary to prevent excessive weight gain and obesity during the later stages of life, especially for females.

Effects of vegetation cover and aquaculture pollution on viral assemblages in mangroves sediments.

Mangrove forests, a critical coastal ecosystem, face numerous anthropogenic threats, particularly from aquaculture activities. Despite the acknowledged significance of viruses in local and global biogeochemical cycles, there is limited knowledge regarding the community structure, genomic diversity, and ecological roles of viruses in mangrove forests ecosystems, especially regarding their responses to aquaculture. In this study, we identified 17,755 viral operational taxonomic units (vOTUs) from nine sediments viromes across three distinct ecological regions of the mangrove forests ecosystem: mangrove, bare flat, and aquaculture regions. Viral assemblages varied among three regions, and the pathogenic viruses associated with marine animals, such as the white spot syndrome virus (WSSV) from Nimaviridae, were identified in this study. The relative abundance of Nimaviridae in the bare flat region was higher than in other regions. Furthermore, viruses in distinct mangrove forests sediments regions have adapted to their environments by adopting distinct survival strategies and encoding various auxiliary metabolic genes involved in carbon metabolism and antibiotic resistance. These adaptations may have profound impacts on biogeochemical cycles. This study provides the first insights into the effects of vegetation cover and aquaculture on the community structure and ecological roles of viruses in mangrove forests sediments. These findings are crucial for understanding the risks posed by anthropogenic threats to mangrove forests ecosystems and informing effective management strategies.

PhyloAln: a convenient reference-based tool to align sequences and high-throughput reads for phylogeny and evolution in the omic era.

The current trend in phylogenetic and evolutionary analyses predominantly relies on omic data. However, prior to core analyses, traditional methods typically involve intricate and time-consuming procedures, including assembly from high-throughput reads, decontamination, gene prediction, homology search, orthology assignment, multiple sequence alignment, and matrix trimming. Such processes significantly impede the efficiency of research when dealing with extensive datasets. In this study, we develop PhyloAln, a convenient reference-based tool capable of directly aligning high-throughput reads or complete sequences with existing alignments as a reference for phylogenetic and evolutionary analyses. Through testing with simulated datasets of species spanning the tree of life, PhyloAln demonstrates consistently robust performance compared with other reference-based tools across different data types, sequencing technologies, coverages, and species, with percent completeness and identity at least 50 percentage points higher in the alignments. Additionally, we validate the efficacy of PhyloAln in removing a minimum of 90% foreign and 70% cross-contamination issues, which are prevalent in sequencing data but often overlooked by other tools. Moreover, we showcase the broad applicability of PhyloAln by generating alignments (completeness mostly larger than 80%, identity larger than 90%) and reconstructing robust phylogenies using real datasets of transcriptomes of ladybird beetles, plastid genes of peppers, or ultraconserved elements of turtles. With these advantages, PhyloAln is expected to facilitate phylogenetic and evolutionary analyses in the omic era. The tool is accessible at https://github.com/huangyh45/PhyloAln.

The phosphatidylethanolamine-binding proteins OsMFT1 and OsMFT2 regulate seed dormancy in rice.

Seed dormancy is crucial for optimal plant life-cycle timing. However, domestication has largely diminished seed dormancy in modern cereal cultivars, leading to challenges such as pre-harvest sprouting (PHS) and subsequent declines in yield and quality. Therefore, it is imperative to unravel the molecular mechanisms governing seed dormancy for the development of PHS-resistant varieties. In this study, we screened a mutant of BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR4 (OsbHLH004) with decreased seed dormancy and revealed that OsbHLH004 directly regulates the expression of 9-CIS-EPOXYCAROTENOID DIOXYGENASE3 (OsNCED3) and GIBBERELLIN 2-OXIDASE6 (OsGA2ox6) in rice (Oryza sativa). Additionally, we determined that two phosphatidylethanolamine-binding proteins, MOTHER OF FT AND TFL1 and 2 (OsMFT1 and OsMFT2; hereafter OsMFT1/2) interact with OsbHLH004 and Ideal Plant Architecture 1 (IPA1) to regulate their binding capacities on OsNCED3 and OsGA2ox6, thereby promoting seed dormancy. Intriguingly, FT-INTERACTING PROTEIN1 (OsFTIP1) interacts with OsMFT1/2 and affects their nucleocytoplasmic translocation into the nucleus, where OsMFT1/2-OsbHLH004 and OsMFT1/2-IPA1 antagonistically modulate the expression of OsNCED3 and OsGA2ox6. Our findings reveal that OsFTIP1-mediated inhibition of nuclear translocation of OsMFT1/2 and the dynamic transcriptional modulation of OsNCED3 and OsGA2ox6 by OsMFT1/2-OsbHLH004 and OsMFT1/2-IPA1 complexes in seed dormancy in rice.

Effects of the combination of various pharmacological treatments and exercise on knee osteoarthritis: a systematic review and network meta-analysis.

Purpose: The combination of pharmacological and non-pharmacological interventions is strongly recommended by current guidelines for knee osteoarthritis. However, few systematic reviews have validated their combined efficacy. In this study, we investigated the effects of the combination of pharmacological agents and exercise on knee osteoarthritis. Methods: Randomized controlled trials that investigated the efficacy of pharmacological agents combined with exercise for knee osteoarthritis were searched in PubMed, Embase, and Cochrane Library up to February 2024. The network meta-analysis was performed within the frequentist framework. Standardized mean difference (SMD) with 95% CI was estimated for pain and function. Grading of recommendations, assessment, development, and evaluations were used to evaluate the certainty of evidence. Results: In total, 71 studies were included. The combination therapy outperformed pharmacological or exercise therapy alone. Among the various pharmacological agents combined with exercise, mesenchymal stem cell injection was ranked the best for short-term pain reduction (SMD: -1.53, 95% CI: -1.92 to -1.13, high certainty), followed by botulinum toxin A, dextrose, and platelet-rich plasma. For long-term pain relief, dextrose prolotherapy was the optimal (SMD: -1.76, 95% CI: -2.65 to -0.88, moderate certainty), followed by mesenchymal stem cells, platelet rich in growth factor, and platelet-rich plasma. Conclusion: Exercise programs should be incorporated into clinical practice and trial design. For patients undergoing exercise therapies, mesenchymal stem cell, dextrose, platelet-rich plasma, platelet rich in growth factor, and botulinum toxin A may be the optimal agents.

Vitamin D alleviation of oxidative stress in human retinal pigment epithelial cells.

BACKGROUND: Oxidative stress-induced retinal pigment epithelium (RPE) cell damage is a major factor in age-related macular degeneration (AMD). Vitamin D3 (VD3) is a powerful antioxidant and it has been suggested to have anti-aging properties and potential for treating AMD. This study aimed to investigate the effect of VD3 on RPE cell oxidative apoptosis of RPE cells in order to provide experimental evidence for the treatment of AMD. METHODS: Human retinal pigment epithelial cell 19 (ARPE-19) cells were divided into four groups: blank group (untreated), model group (incubated in medium with 400 µmol/L H2O2 for 1 h), VD3 group (incubated in medium with 100 µmol/L VD3 for 24 h), and treatment group (incubated in medium with 400 µmol/L H2O2 for 1 h and 100 µmol/L VD3 for 24 h). Cell viability, cell senescence, ROS content, expression levels of vitamin D specific receptors, Akt, Sirt1, NAMPT, and JNK mRNA expression levels, SOD activity, and MDA, GSH, and GPX levels were measured. RESULTS: We first established an ARPE-19 cell stress model with H2O2. Our control experiment showed that VD3 treatment had no significant effect on ARPE-19 cell viability within 6-48 h. Treating the stressed ARPE-19 cells with VD3 showed mixed results; caspase-3 expression was decreased, Bcl-2 expression was increased, MDA level of ARPE-19 cells was decreased, GSH-PX, GPX and SOD levels were increased, the relative mRNA expression levels of Akt, Sirt1, NAMPT were increased (P < 0.05), and the relative mRNA expression level of JNK was decreased (P < 0.05). CONCLUSION: VD3 can potentially slow the development of AMD.