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Human immunodeficiency virus (HIV) infection and the acquired immune deficiency syndrome (AIDS) exhibit variable patterns among the provinces of China. Knowledge of the geographical distribution of the HIV/AIDS epidemic is needed for the prevention and control of AIDS. Thus, the cumulative number of reported cases of HIV/AIDS from the period 1985-2013, and the incidence rate of AIDS in 2013 were determined. Spatial autocorrelation analysis and hotspot analysis were conducted using ArcGIS10.2 to explore the spatial distribution of the HIV/AIDS epidemic. Both the thematic map and the global spatial autocorrelation Moran’s I statistics revealed a clustered distribution of the spatial pattern. A local spatial autocorrelation analysis indicated hotspots of AIDS incidence rate that were confined to the provinces of Guangxi, Yunnan and Sichuan. The hotspots encompassed Guangxi and Yunnan, while Henan Province displayed a negative autocorrelation with more variable numbers that included neighbouring regions. The Getis-Ord Gi* statistics identified 6 hotspots and 8 coldspots for the incidence of AIDS, and 7 hotspots and 1 coldspot for the cumulative number of reported cases of HIV/AIDS. The spatial distribution pattern of the HIV/AIDS epidemic in China is clustered, demonstrating hotspots located in the Southwest. Specific interventions targeting provinces with severe HIV/AIDS epidemic are urgently needed.

Maternal syphilis not only seriously affects the quality of life of pregnant women themselves but also may cause various adverse pregnancy outcomes (APOs). This study aimed to analyse the association between the related factors and APOs in maternal syphilis. 7,030 pregnant women infected with syphilis in Henan Province between January 2016 and December 2022 were selected as participants. Information on their demographic and clinical characteristics, treatment status, and pregnancy outcomes was collected. Multivariate logistic regression models and chi-squared automatic interaction detector (CHAID) decision tree models were used to analyse the factors associated with APOs. The multivariate logistic regression results showed that the syphilis infection history (OR = 1.207, 95% CI, 1.035–1.409), the occurrence of abnormality during pregnancy (OR = 5.001, 95% CI, 4.203–5.951), not receiving standard treatment (OR = 1.370, 95% CI, 1.095–1.716), not receiving any treatment (OR = 1.313, 95% CI, 1.105–1.559), and a titre ≥1:8 at diagnosis (OR = 1.350, 95%CI, 1.079–1.690) and before delivery (OR = 1.985, 95%CI, 1.463–2.694) were risk factors. A total of six influencing factors of APOs in syphilis-infected women were screened using the CHAID decision tree model. Integrated prevention measures such as early screening, scientific eugenics assessment, and standard syphilis treatment are of great significance in reducing the incidence of APOs for pregnant women infected with syphilis.

Visualization of specific genomic loci in live cells is a prerequisite for the investigation of dynamic changes in chro- matin architecture during diverse biological processes, such as cellular aging. However, current precision genomic imaging methods are hampered by the lack of fluorescent probes with high specificity and signal-to-noise contrast. We find that conventional transcription activator-like effectors （TALEs） tend to form protein aggregates, thereby compromising their performance in imaging applications. Through screening, we found that fusing thioredoxin with TALEs prevented aggregate formation, unlocking the full power of TALE-based genomic imaging. Using thioredoxin-fused TALEs （TTALEs）, we achieved high-quality imaging at various genomic loci and observed aging-associated （epi） genomic alterations at telomeres and centromeres in human and mouse premature aging models. Importantly, we identified attrition of ribosomal DNA repeats as a molecular marker for human aging. Our study establishes a simple and robust imaging method for precisely monitoring chromatin dynamics in vitro and in vivo.

Layered double hydroxides are promising candidates for the electrocatalytic oxygen evolution reaction. Unfortunately, their catalytic kinetics and long-term stabilities are far from satisfactory compared to those of rare metals. Here, we investigate the durability of nickel-iron layered double hydroxides and show that ablation of the lamellar structure due to metal dissolution is the cause of the decreased stability. Inspired by the amino acid residues in photosystem II, we report a strategy using trimesic acid anchors to prepare the subsize nickel-iron layered double hydroxides with kinetics, activity and stability superior to those of commercial catalysts. Fundamental investigations through operando spectroscopy and theoretical calculations reveal that the superaerophobic surface facilitates prompt release of the generated O 2 bubbles, and protects the structure of the catalyst. Coupling between the metals and coordinated carboxylates via C‒O‒Fe bonding prevents dissolution of the metal species, which stabilizes the electronic structure by static coordination. In addition, the uncoordinated carboxylates formed by dynamic evolution during oxygen evolution reaction serve as proton ferries to accelerate the oxygen evolution reaction kinetics. This work offers a promising way to achieve breakthroughs in oxygen evolution reaction stability and dynamic performance by introducing functional ligands with static and dynamic compatibilities. Layered double hydroxides are promising candidates for electrocatalytic oxygen evolution reaction yet their catalytic stability needs to be further improved. Here, the authors use trimesic acid anchoring to stabilize nickel-iron layered hydroxides for water oxidation with enhanced stability.

Psoriasis is a chronic inflammatory skin disease occurring worldwide, with multiple systemic complications, which seriously affect the quality of life and physical and mental health of patients. The pathogenesis of psoriasis is related to the environment, genetics, epigenetics, and dysregulation of immune cells such as T cells, dendritic cells (DCs), and nonimmune cells such as keratinocytes. Absent in melanoma 2 ( AIM2 ), a susceptibility gene locus for psoriasis, has been strongly linked to the genetic and epigenetic aspects of psoriasis and increased in expression in psoriatic keratinocytes. AIM2 was found to be activated in an inflammasome-dependent way to release IL-1β and IL-18 to mediate inflammation, and to participate in immune regulation in psoriasis, or in an inflammasome-independent way by regulating the function of regulatory T(Treg) cells or programming cell death in keratinocytes as well as controlling the proliferative state of different cells. AIM2 may also play a role in the recurrence of psoriasis by trained immunity. In this review, we will elaborate on the characteristics of AIM2 and how AIM2 mediates the development of psoriasis.

Organic batteries free of toxic metal species could lead to a new generation of consumer energy storage devices that are safe and environmentally benign. However, the conventional organic electrodes remain problematic because of their structural instability, slow ion-diffusion dynamics and poor electrical conductivity. Here, we report on the development of a redox-active, crystalline, mesoporous covalent organic framework (COF) on carbon nanotubes for use as electrodes; the electrode stability is enhanced by the covalent network, the ion transport is facilitated by the open meso-channels and the electron conductivity is boosted by the carbon nanotube wires. These effects work synergistically for the storage of energy and provide lithium-ion batteries with high efficiency, robust cycle stability and high rate capability. Our results suggest that redox-active COFs on conducting carbons could serve as a unique platform for energy storage and may facilitate the design of new organic electrodes for high-performance and environmentally benign battery devices.

Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3–14 doses/person). In total, 12–30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1–2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.

DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8 dex2 ) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its microRNA-processing activity. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1γ. Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8 dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and mouse osteoarthritis. Taken together, these analyses uncovered a novel, microRNA processing-independent role in maintaining heterochromatin organization and attenuating senescence by DGCR8, thus representing a new therapeutic target for alleviating human aging-related disorders. DGCR8 is a component of the canonical microprocessor complex for microRNA biogenesis. Here the authors implicate DGCR8 in heterochromatin maintenance and aging attenuation independent of its miRNA-processing activity through Lamin B1, KAP1 and HP1 interaction. DGCR8 overexpression can alleviate aging and senescence

Oxidative stress is an imbalance between free radicals and the antioxidant system causing overgeneration of free radicals (oxygen-containing molecules) ultimately leading to oxidative damage in terms of lipid peroxidation, protein denaturation, and DNA mutation. Oxidative stress can activate autophagy to alleviate oxidative damage and maintain normal physiological activities of cells by degrading damaged organelles or local cytoplasm. When oxidative stress is not eliminated by autophagy, it activates the apoptosis cascade. This review provides a brief summary of mitochondrial-endoplasmic reticulum communication-mediated oxidative stress and autophagy. Mitochondria and endoplasmic reticulum being important organelles in cells are directly or indirectly connected to each other through mitochondria-associated endoplasmic reticulum membranes and jointly regulate oxidative stress and autophagy. The reactive oxygen species (ROS) produced by the mitochondrial respiratory chain are the main inducers of oxidative stress. Damaged mitochondria can be effectively cleared by the process of mitophagy mediated by PINK1/parkin pathway, Nix/BNIP3 pathways, and FUNDC1 pathway, avoiding excessive ROS production. However, the mechanism of mitochondrial-endoplasmic reticulum communication in the regulation of oxidative stress and autophagy is rarely known. For this reason, this review explores the mutual connection of mitochondria and endoplasmic reticulum in mediating oxidative stress and autophagy through ROS and Ca2+ and aims to provide part of the theoretical basis for alleviating oxidative stress through autophagy mediated by mitochondrial-endoplasmic reticulum communication.

Therapeutic genome editing requires effective and targeted delivery methods. The delivery of Cas9 mRNA using adeno-associated viruses has led to potent in vivo therapeutic efficacy, but can cause sustained Cas9 expression, anti-Cas9 immune responses and off-target edits. Lentiviral vectors have been engineered to deliver nucleases that are expressed transiently, but in vivo evidence of their biomedical efficacy is lacking. Here, we show that the lentiviral codelivery of Streptococcus pyogenes Cas9 mRNA and expression cassettes that encode a guide RNA that targets vascular endothelial growth factor A ( Vegfa ) is efficacious in a mouse model of wet age-related macular degeneration induced by Vegfa . A single subretinal injection of engineered lentiviruses knocked out 44% of Vegfa in retinal pigment epithelium and reduced the area of choroidal neovascularization by 63% without inducing off-target edits or anti-Cas9 immune responses. Engineered lentiviruses for the transient expression of nucleases may form the basis of new treatments for retinal neovascular diseases. Lentiviruses co-packaging Sp Cas9 mRNA and an expression cassette encoding for a guide RNA targeting the Vegfa gene prevent mice from developing wet age-related macular degeneration induced by Vegfa . [Summary amended to correct the description of the packaged cargo.]