Kv3.3 Channels Bind Hax-1 and Arp2/3 to Assemble a Stable Local Actin Network that Regulates Channel Gating.

Mutations in the Kv3.3 potassium channel (KCNC3) cause cerebellar neurodegeneration and impair auditory processing. The cytoplasmic C terminus of Kv3.3 contains a proline-rich domain conserved in proteins that activate actin nucleation through Arp2/3. We found that Kv3.3 recruits Arp2/3 to the plasma membrane, resulting in formation of a relatively stable cortical actin filament network resistant to cytochalasin D that inhibits fast barbed end actin assembly. These Kv3.3-associated actin structures are required to prevent very rapid N-type channel inactivation during short depolarizations of the plasma membrane. The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3. A human Kv3.3 mutation within a conserved proline-rich domain produces channels that bind Hax-1 but are impaired in recruiting Arp2/3 to the plasma membrane, resulting in growth cones with deficient actin veils in stem cell-derived neurons.

Glioblastoma remodelling of human neural circuits decreases survival.

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

Wolbachia mediates crosstalk between miRNA and Toll pathways to enhance resistance to dengue virus in Aedes aegypti.

The obligate endosymbiont Wolbachia induces pathogen interference in the primary disease vector Aedes aegypti, facilitating the utilization of Wolbachia-based mosquito control for arbovirus prevention, particularly against dengue virus (DENV). However, the mechanisms underlying Wolbachia-mediated virus blockade have not been fully elucidated. Here, we report that Wolbachia activates the host cytoplasmic miRNA biogenesis pathway to suppress DENV infection. Through the suppression of the long noncoding RNA aae-lnc-2268 by Wolbachia wAlbB, aae-miR-34-3p, a miRNA upregulated by the Wolbachia strains wAlbB and wMelPop, promoted the expression of the antiviral effector defensin and cecropin genes through the Toll pathway regulator MyD88. Notably, anti-DENV resistance induced by Wolbachia can be further enhanced, with the potential to achieve complete virus blockade by increasing the expression of aae-miR-34-3p in Ae. aegypti. Furthermore, the downregulation of aae-miR-34-3p compromised Wolbachia-mediated virus blockade. These findings reveal a novel mechanism by which Wolbachia establishes crosstalk between the cytoplasmic miRNA pathway and the Toll pathway via aae-miR-34-3p to strengthen antiviral immune responses against DENV. Our results will aid in the advancement of Wolbachia for arbovirus control by enhancing its virus-blocking efficiency.

Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance.

The intrinsic electrical characteristics of different types of neurons are shaped by the K+ channels they express. From among the more than 70 different K+ channel genes expressed in neurons, Kv3 family voltage-dependent K+ channels are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. In general, the four Kv3 channels Kv3.1-Kv3.4 share the property of activating and deactivating rapidly at potentials more positive than other channels. Each Kv3 channel gene can generate multiple protein isoforms, which contribute to the high-frequency firing of neurons such as auditory brain stem neurons, fast-spiking GABAergic interneurons, and Purkinje cells of the cerebellum, and to regulation of neurotransmitter release at the terminals of many neurons. The different Kv3 channels have unique expression patterns and biophysical properties and are regulated in different ways by protein kinases. In this review, we cover the function, localization, and modulation of Kv3 channels and describe how levels and properties of the channels are altered by changes in ongoing neuronal activity. We also cover how the protein-protein interaction of these channels with other proteins affects neuronal functions, and how mutations or abnormal regulation of Kv3 channels are associated with neurological disorders such as ataxias, epilepsies, schizophrenia, and Alzheimer's disease.

An overview of systematic reviews of clinical studies of platelet-rich plasma for venous ulcers.

To evaluate the clinical evidence of platelet-rich plasma (PRP) in the treatment of venous ulcers (VUs). Electronic searches were conducted through the Cochrane Library, Web of Science, Embase and PubMed. AMSTAR-2 was used to assess the methodological quality. The quality of evidence was assessed using the GRADE system. According to AMSTAR-2, the methodological quality of the included reviews was generally inadequate owing to the limitations of entries 2, 4 and 7. Due to bias risk and imprecision, the evidence quality of the outcome measures was inadequate. In conclusion, PRP may have a therapeutic effect on VUs. However, this conclusion must be treated with caution due to methodological flaws of the included systematic reviews and meta-analyses.

Quality of evidence supporting the role of hyperbaric oxygen therapy for diabetic foot ulcers.

The goal of this overview of systematic reviews (SRs) and meta-analyses (MAs) was to methodically gather, evaluate and summarize the data supporting the use of hyperbaric oxygen therapy (HBOT) to treat diabetic foot ulcers (DFUs). The Cochrane Library, Embase, PubMed, Web of Science and Embase were all searched thoroughly to identify SRs/MAs that qualified. AMSTAR-2 tool, PRISMA checklists and GRADE system were applied by two reviewers independently to assess the methodological quality, reporting and evidence quality of the included SRs/MAs, respectively. Eleven SRs/MAs were enrolled in this overview. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the limitations of items 2, 4 and 7. For the PRISMA, the overall quality of reporting is not satisfactory due to missing reporting on protocol, search, as well as additional analysis. The majority of outcomes had low- to moderate-quality evidence, and no high-quality evidence was found to support the role of HBOT for DFUs, according to GRADE. To conclude, the potential of HBOT in treating DFUs is supported by evidence of low to moderate quality. More rigorously designed, high-level studies are needed in the future to determine the evidence for HBOT for DFU, including the timing, frequency and duration of HBOT interventions.

Treatment of diabetic foot with moxibustion: Clinical evidence from meta-analysis.

To assess the efficacy of moxibustion for diabetic foot, and compile the findings of randomised clinical trials. China National Knowledge Infrastructure Database, Medicine, WanFang Database, Embase, Chinese Scientific Journal Database and Web of Science were from the establishment to January, 2024 were searched. Randomised controlled trials, which evaluated the effects of moxibustion were included. A total of 12 randomised controlled trials involving 1196 patients were included. According to the pooled results of this meta-analysis, effective rate (relative risk 1.16, 95% confidence intervals, CI [1.11, 1.22]), healing time (mean difference [MD] -6.27, 95% CI [-8.68, -3.86]), wound area (MD 3.46, 95% CI [0.84, 6.09]), and ankle brachial index (MD 0.14, 95% CI [0.03, 0.24]) were statistically significant compared to the control group. This study suggests that moxibustion treatment has the potential for improving symptoms of diabetic foot. However, future in-depth research on the benefits and harms of moxibustion for the diabetic foot is needed before it can be accepted as an evidence-based treatment.

DNA methylome and transcriptome identified Key genes and pathways involved in Speckled Eggshell formation in aged laying hens.

BACKGROUND: The quality of poultry eggshells is closely related to the profitability of egg production. Eggshell speckles reflect an important quality trait that influences egg appearance and customer preference. However, the mechanism of speckle formation remains poorly understood. In this study, we systematically compared serum immune and antioxidant indices of hens laying speckled and normal eggs. Transcriptome and methylome analyses were used to elucidate the mechanism of eggshell speckle formation. RESULTS: The results showed that seven differentially expressed genes (DEGs) were identified between the normal and speckle groups. Gene set enrichment analysis (GSEA) revealed that the expressed genes were mainly enriched in the calcium signaling pathway, focal adhesion, and MAPK signaling pathway. Additionally, 282 differentially methylated genes (DMGs) were detected, of which 15 genes were associated with aging, including ARNTL, CAV1, and GCLC. Pathway analysis showed that the DMGs were associated with T cell-mediated immunity, response to oxidative stress, and cellular response to DNA damage stimulus. Integrative analysis of transcriptome and DNA methylation data identified BFSP2 as the only overlapping gene, which was expressed at low levels and hypomethylated in the speckle group. CONCLUSIONS: Overall, these results indicate that aging- and immune-related genes and pathways play a crucial role in the formation of speckled eggshells, providing useful information for improving eggshell quality.

Facet-Dependent Passivation for Efficient Perovskite Solar Cells.

Understanding the interplay between the surface structure and the passivation materials and their effects associated with surface structure modification is of fundamental importance; however, it remains an unsolved problem in the perovskite passivation field. Here, we report a surface passivation principle for efficient perovskite solar cells via a facet-dependent passivation phenomenon. The passivation process selectively occurs on facets, which is observed with various post-treatment materials with different functionality, and the atomic arrangements of the facets determine the alignments of the passivation layers. The profound understanding of facet-dependent passivation leads to the finding of 2-amidinopyridine hydroiodide as the material for a uniform and effective passivation on both (100) and (111) facets. Consequently, we achieved perovskite solar cells with an efficiency of 25.10% and enhanced stability. The concept of facet-dependent passivation can provide an important clue on unidentified passivation principles for perovskite materials and a novel means to enhance the performance and stability of perovskite-based devices.

Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer's disease: a randomized phase 1 study.

BACKGROUND: AD16 is a Class 1.1 new drug candidate for Alzheimer's disease (AD), which has demonstrated potential benefits in AD by reducing neuroinflammation in preclinical studies. Herein, the pharmacokinetics (PK), safety, and tolerability of single and multiple-dose AD16 and the effect of food were assessed in healthy Chinese adults. METHODS: Single-center, randomized, placebo-controlled, double-blind studies were conducted for single and multiple ascending doses. A total of 62 subjects were enrolled in single-dose groups; 10 each in 5, 10, 20, 30, and 40 mg groups, and 6 each in 60 and 80 mg dose groups. Twenty subjects were divided equally into 30 and 40 mg groups for the multiple-dose study. To determine the effect of a high-fat diet on AD16, 16 subjects were administered a single 20 mg dose of AD16 under the fasted and fed condition in a single-center, randomized, open-label, two-cycle, two-crossover study. Moreover, safety and PK parameters were also assessed. RESULTS: Plasma exposure to a single oral dose of AD16 increased at an approximate dose-increasing rate. The pharmacodynamic dose of the AD16 can be maintained through the accumulation effect of the drug within the safety window. Compared to fasting, ingesting a high-fat meal decelerated the rate of AD16 absorption, albeit without effect on its overall absorption. No dose-related toxicities were seen in any of the studies, all treatment-emergent adverse events were grade I/II, and no serious adverse event occurred. CONCLUSIONS: The present study exhibited favorable safety, tolerability, and PK profile of AD16, supporting its further research as a potential drug treatment for AD. TRIAL REGISTRATION: ClinicalTrials.gov; NCT05787028, NCT05787041, NCT05806177. The SAD and FE studies were retrospectively registered on 28 March 2023. The MAD study was retrospectively registered on 10 April 2023.

"De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade.

Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p < 0.01). All tumors had histologic features of the giant cell variant of glioblastoma. They lacked EGFR amplification, lacked combined trisomy of chromosome 7 plus monosomy of chromosome 10, and only rarely had TERT promoter mutation or CDKN2A homozygous deletion, which are hallmarks of conventional IDH-wildtype glioblastoma. Instead, they harbored frequent inactivating mutations in TP53, NF1, PTEN, ATRX, and SETD2 and recurrent activating mutations in PDGFRA. DNA methylation profiling revealed they did not align with known reference adult glioblastoma methylation classes, but instead had unique globally hypomethylated epigenomes and mostly classified as "Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass A". Five patients were treated with immune checkpoint blockade, four of whom survived greater than 3 years. The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.

Long non-coding RNA LUCAT1 regulates the RAS pathway to promote the proliferation and invasion of malignant glioma cells through ABCB1.

Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of tumors and have gradually become a hot topic in the field of glioma research in recent years. In this study, the role of lung cancer associated transcript 1 (lncRNA LUCAT 1) in glioma occurrence and development, as well as its possible regulatory mechanism, was explored. We utilized the gene chip technology in the preliminary experiment, and based on the experiment results, selected LUCAT1（NONHSAT102745）, which was significantly upregulated in glioma, and ATP-binding cassette Subfamily B member l (ABCB1), which was significantly down-regulated in co-expression analysis, for study. Next, the expression of LUCAT1 and ABCB1 in cells and tissues was immediately evaluated. Subsequently, the cells were transfected with scrambled siRNA, LUCAT1-siRNA/ABCB 1-siRNA, or overexpressed LUCAT1/ABCB1 plasmid + RAS signaling pathway inhibitor-farnesylthiosalicylic acid (FTS). By comparing with the normal combination negative control group, the cell proliferation and invasion ability were evaluated. Finally, subcutaneous tumor formation experiments in the nude mice confirmed the association between LUCAT1 and ABCB1 and RAS signaling pathways. The expression of LUCAT 1 was up-regulated with an increase in WHO grade, and the lncRNA-mRNA co-expression analysis showed that the expression of ABCB1 was low. LUCAT 1 gene knockout reduced the mRNA and protein levels of Ras signaling pathway related factors (Ras, Raf-1, p-AKT, and p-ERK) as regulating ABCB1 expression and inhibiting the ability of tumor in proliferation and invasion no matter in vitro or in vivo. For overexpressing of LUCAT 1, the opposite was true. After we knocked out ABCB1, the LUCAT1 expression was reversely regulated while the level of RAS signaling pathway related factors increased, and the ability of tumors in proliferation and invasion was enhanced. The abnormal LUCAT1 expression affected the biological behaviors of glioma cells, such as proliferation, invasion, etc. by regulating ABCB1 and promoting the activation of the RAS signaling pathway. This provided a new drug target and therapeutic approach for gene therapy of glioma, which is expected to significantly improve the prognosis of relevant patients.

Privacy Risk Assessment of Smart Home System Based on a STPA-FMEA Method.

Although the smart home industry is rapidly emerging, it faces the risk of privacy security that cannot be neglected. As this industry now has a complex combination system involving multiple subjects, it is difficult for the traditional risk assessment method to meet these new security requirements. In this study, a privacy risk assessment method based on the combination of system theoretic process analysis-failure mode and effect analysis (STPA-FMEA) is proposed for a smart home system, considering the interaction and control of 'user-environment-smart home product'. A total of 35 privacy risk scenarios of 'component-threat-failure-model-incident' combinations are identified. The risk priority numbers (RPN) was used to quantitatively assess the level of risk for each risk scenario and the role of user and environmental factors in influencing the risk. According to the results, the privacy management ability of users and the security state of the environment have significant effects on the quantified values of the privacy risks of smart home systems. The STPA-FMEA method can identify the privacy risk scenarios of a smart home system and the insecurity constraints in the hierarchical control structure of the system in a relatively comprehensive manner. Additionally, the proposed risk control measures based on the STPA-FMEA analysis can effectively reduce the privacy risk of the smart home system. The risk assessment method proposed in this study can be widely applied to the field of risk research of complex systems, and this study can contribute to the improvement of privacy security of smart home systems.

Systematic Selection Signature Analysis of Chinese Gamecocks Based on Genomic and Transcriptomic Data.

Selection pressures driven by natural causes or human interference are key factors causing genome variants and signatures of selection in specific regions of the genome. Gamecocks were bred for cockfighting, presenting pea-combs, larger body sizes, stronger limbs, and higher levels of aggression than other chickens. In this study, we aimed to explore the genomic differences between Chinese gamecocks and commercial, indigenous, foreign, and cultivated breeds by detecting the regions or sites under natural or artificial selection using genome-wide association studies (GWAS), genome-wide selective sweeps based on the genetic differentiation index (FST), and transcriptome analyses. Ten genes were identified using GWAS and FST: gga-mir-6608-1, SOX5, DGKB, ISPD, IGF2BP1, AGMO, MEOX2, GIP, DLG5, and KCNMA1. The ten candidate genes were mainly associated with muscle and skeletal development, glucose metabolism, and the pea-comb phenotype. Enrichment analysis results showed that the differentially expressed genes between the Luxi (LX) gamecock and Rhode Island Red (RIR) chicken were mainly related to muscle development and neuroactive-related pathways. This study will help to understand the genetic basis and evolution of Chinese gamecocks and support the further use of gamecocks as an excellent breeding material from a genetic perspective.

Auditory brainstem development of naked mole-rats (Heterocephalus glaber).

Life underground often leads to animals having specialized auditory systems to accommodate the constraints of acoustic transmission in tunnels. Despite living underground, naked mole-rats use a highly vocal communication system, implying that they rely on central auditory processing. However, little is known about these animals' central auditory system, and whether it follows a similar developmental time course as other rodents. Naked mole-rats show slowed development in the hippocampus suggesting they have altered brain development compared to other rodents. Here, we measured morphological characteristics and voltage-gated potassium channel Kv3.3 expression and protein levels at different key developmental time points (postnatal days 9, 14, 21 and adulthood) to determine whether the auditory brainstem (lateral superior olive and medial nucleus of the trapezoid body) develops similarly to two common auditory rodent model species: gerbils and mice. Additionally, we measured the hearing onset of naked mole-rats using auditory brainstem response recordings at the same developmental timepoints. In contrast with other work in naked mole-rats showing that they are highly divergent in many aspects of their physiology, we show that naked mole-rats have a similar hearing onset, between postnatal day (P) 9 and P14, to many other rodents. On the other hand, we show some developmental differences, such as a unique morphology and Kv3.3 protein levels in the brainstem.

Suppression of Kv3.3 channels by antisense oligonucleotides reverses biochemical effects and motor impairment in spinocerebellar ataxia type 13 mice.

Mutations in KCNC3, the gene that encodes the Kv3.3 voltage dependent potassium channel, cause Spinocerebellar Ataxia type 13 (SCA13), a disease associated with disrupted motor behaviors, progressive cerebellar degeneration, and abnormal auditory processing. The Kv3.3 channel directly binds Hax-1, a cell survival protein. A disease-causing mutation, Kv3.3-G592R, causes overstimulation of Tank Binding Kinase 1 (Tbk1) in the cerebellum, resulting in the degradation of Hax-1 by promoting its trafficking into multivesicular bodies and then to lysosomes. We have now tested the effects of antisense oligonucleotides (ASOs) directed against the Kv3.3 channel on both wild type mice and those bearing the Kv3.3-G592R-encoding mutation. Intracerebroventricular infusion of the Kcnc3-specific ASO suppressed both mRNA and protein levels of the Kv3.3 channel. In wild-type animals, this produced no change in levels of activated Tbk1, Hax-1 or Cd63, a tetraspanin marker for late endosomes/multivesicular bodies. In contrast, in mice homozygous for the Kv3.3-G592R-encoding mutation, the same ASO reduced Tbk1 activation and levels of Cd63, while restoring the expression of Hax-1 in the cerebellum. The motor behavior of the mice was tested using a rotarod assay. Surprisingly, the active ASO had no effects on the motor behavior of wild type mice but restored the behavior of the mutant mice to those of age-matched wild type animals. Our findings indicate that, in mature intact animals, suppression of Kv3.3 expression can reverse the deleterious effects of a SCA13 mutation while having little effect on wild type animals. Thus, targeting Kv3.3 expression may prove a viable therapeutic approach for SCA13.

The association between hypertension and the risk of gallstone disease: a cross-sectional study.

BACKGROUND: To explore the association between hypertension and the risk of gallstone disease. METHODS: We collected the data about the subjects receiving physical examination. Gallstone disease was diagnosed by abdominal ultrasound. Multivariable logistic regression was used to study the association between blood pressure and the risk of gallstone disease. SPSS version 23.0 was used for statistical analysis, and two-tailed P < 0.05 was defined as statistically significant. RESULTS: A total of 318,403 people were included in the study and 171,276 (53.8%) of them were men and 147,127 (46.2%) were women. Among them, 27,463 (8.6%) were diagnosed with gallstone disease on ultrasound examination, with 12,452 (3.9%) cases of gallstones and 15,017 (4.7%) cases of cholecystectomy. Multivariable logistic regression showed that hypertension was significantly associated with the risk of gallstone disease (OR = 1.05; 95% CI: 1.02-1.10; P = 0.03) and gallstones (OR = 1.12; 95% CI: 1.06-1.19; P < 0.01) and the association between hypertension and gallstone disease was stronger in women than in men. However, hypertension was not significantly correlated with cholecystectomy (OR = 0.99; 95% CI: 0.95-1.04; P = 0.85). Additionally, results showed that with the severity of hypertension increased, the risk of gallstone disease was also marked elevated (P for trend < 0.001). CONCLUSIONS: The gallstone disease was prevalent and hypertension is significantly associated with the gallstone disease risk with a significant dose-response association. This study showed that the association between hypertension and cholecystectomy was not statistically significant, maybe hypertension correlated with gallstones but not with symptomatic gallstone disease which would require cholecystectomy.

Icariin inhibits epithelial mesenchymal transition of renal tubular epithelial cells via regulating the miR-122-5p/FOXP2 axis in diabetic nephropathy rats.

Epithelial mesenchymal transition (EMT) of renal tubular epithelial cells (RTECs) dominates the pathology of diabetic nephropathy (DN). microRNAs (miRNAs) can influence the fate of DN via regulation of EMT. This study aimed to analyze the role of Icariin (ICA) in EMT of RTECs, hoping to provide theoretical basis for DN management. The DN rat model was established using streptozocin, followed by ICA treatment, histopathological observation, and detection of creatinine and blood urea nitrogen. In vitro cell models were established using high glucose (HG), followed by assessment of cell proliferation, apoptosis, and migration, and E-cadherin, α-SMA, miR-122-5p, and FOXP2 expressions. Cells were transfected with miR-122-5p mimics or si-FOXP2 for joint experiments with ICA. The targeting relationship between miR-122-5p and FOXP2 was verified. ICA repaired renal dysfunctions and glomerular structure abnormities of DN rats in a dose-dependent manner. In vitro, ICA improved proliferation while suppressed migration, apoptosis, and EMT of RTECs. miR-122-5p was up-regulated in DN rats and suppressed by ICA, and miR-122-5p targeted FOXP2. miR-122-5p up-regulation or FOXP2 down-regulation reversed the protective effects of ICA on HG-induced RTECs. Overall, our finding ascertained that ICA inhibited miR-122-5p to promote FOXP2 transcription, thereby attenuating EMT of RTECs and renal injury in DN rats.

Insights into the photocatalytic activation of peroxymonosulfate by visible light over BiOBr-cyclodextrin polymer complexes for efficient degradation of dye pollutants in water.

The combination of adsorption-photocatalysis and advanced oxidation processes (AOP) based on sulfate (SO4•-) for the treatment of organic pollution has the advantages of a high degradation rate, affordability, and an absence of secondary pollution. This study combined amphiphilic super-crosslinked porous cyclodextrin resin (PBCD-B-D), bismuth oxybromide (BiOBr), a composite material with dual functions of adsorption and photocatalysis, and AOP based on SO4•- for the treatment of Acid Orange 7 (AO7) in water. The combination of BiOBr/PBCD-B-D (BOP-24) with peroxymonosulfate (PMS) showed an optimal adsorption-photocatalytic effect. Compared to the 24% PBCD-B-D (BOP-24)/visible light system, the degradation efficiency of BOP-24/PMS system for AO7 is increased from 64.1% to 99.2% within shorter time (∼60 min). Moreover, the BOP-24/PMS system showed a wide range of pH application (pH = 3-11). The addition of Cl-, SO42-, and NO3- promoted the photodegradation of AO7, whereas the addition of CO32- did not. The free radical capture experiments of the BOP-24/PMS AO7 degradation system showed that •O2-, h+, •OH, and SO4•- are reactive species. The proposed BOP-24 system used adsorption and a unique cavity structure to enrich AO7 near the active site, thereby reducing the path for PMS activation. PMS also acted as an electron (e-) acceptor to promote the transfer of part of e- to PMS, thereby further improving the efficiency of carrier separation. The proposed system is an effective method to improve the degradation of pollutants and broadens the range of application of SO4•--based AOP technology.

Effect of mutations across reverse transcriptase region on HBV replication and progression of liver diseases in Chinese patients.

It was known that mutations in the RT region were mainly related to nucleot(s)ide analogs resistance. Increasing studies indicated that RT mutations were related to advanced liver diseases (ALD) and had effects on HBV replication, but the distribution characteristics of mutations across RT region in the development of liver diseases and the effect of RT mutations on HBV replication were not fully clarified. HBV RT region was direct-sequenced in 1473 chronic HBV-infected patients. Mutation frequencies were analyzed to identify the specific mutations differing between groups classified by genotypes, loads of HBV DNA, or progression of liver diseases. In the range of rt145-rt290, rt145, rt221, rt222, rt267, and rt271 were the genotype-polymorphic sites, while rt238 was the genotype-specific sites. Mutations at rt163, rt173, rt180, rt181, rt184, rt191, rt199, and rt214 were more frequent among patients with C-genotype HBV, while those at rt220, rt225, rt226, rt269, and rt274 were more frequent among patients with B-genotype HBV. RtM204V/I could reduce the HBV DNA loads while rtQ/L267H/R could increase the HBV DNA loads. RtV214A/E/I (OR 3.94, 95% CI 1.09 to 14.26) was an independent risk factor for advanced liver diseases. In summary, the hotspots of mutations were different between B and C genotypes. Besides the effect on the S region, RT mutations had effects on HBV replication by other unknown ways. RtV214A/E/I was found to be an independent risk factor for ALD, suggesting that mutations at rt214 site could be used as a potential virological marker for the liver disease progression.