Trends in the burden and determinants of HIV in the Asia-Pacific region (1990-2019): An age-period-cohort analysis of the 2019 Global Burden of Disease Study.

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.

Hsa_circ_0049472 contributed to amyloid-beta peptide-induced neurotoxicity, apoptosis and inflammation via regulating PI3K-AKT signaling pathway by interacting with miR-22-3p/ZNF217 axis.

BACKGROUND: Circular RNAs (circRNAs) exhibited important roles in Alzheimer's disease (AD). Here, we focused on the dysregulation of hsa_circ_0049472 (circ_0049472) and potential functions in SK-N-SH cells with amyloid-beta peptide (Aß) treatment in AD. METHODS: RNA expression was detected by real-time quantitative PCR. Cell viability and proliferation were measured by MTS and Edu assays. Flow cytometry was used for apoptosis detection, and cell inflammation was assessed using enzyme-linked immunosorbent assay. Target interaction was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Protein expression and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathway were examined by Immunoblotting. RESULTS: Aß treatment inhibited cell viability and proliferation of SK-N-SH cells, but enhanced apoptosis rate, apoptosis protein levels (Bcl2-associated X protein and cleaved-caspase-3) and inflammatory cytokines (interleukin -6, IL-1ß, tumor necrosis factor-α). Then, circ_0049472 expression was shown to be upregulated in response to Aß stimulation and knockdown of circ_0049472 has ameliorated Aß-induced cell injury. Circ_0049472 was identified as a sponge for miR-22-3p, and miR-22-3p inhibition reversed the regulation of circ_0049472 knockdown in Aß-treated cells. Furthermore, ZNF217 acted as a target of miR-22-3p and circ_0049472 could regulate ZNF217 expression via binding to miR-22-3p. Overexpression of miR-22-3p abated Aß-induced apoptosis and inflammation via downregulating ZNF217. Furthermore, Aß reduced proteins levels of p-PI3K and p-AKT, and this inhibition of PI3K-AKT pathway was restored by the regulation of circ_0049472/miR-22-3p/ZNF217 axis. CONCLUSION: Circ_0049472 was involved in Aß-induced neural injury by regulating miR-22-3p/ZNF217 axis to affect PI3K-AKT pathway. This study has discovered an innovative mechanism for AD.

Recent Advance in Synaptic Plasticity Modulation Techniques for Neuromorphic Applications.

Manipulating the expression of synaptic plasticity of neuromorphic devices provides fascinating opportunities to develop hardware platforms for artificial intelligence. However, great efforts have been devoted to exploring biomimetic mechanisms of plasticity simulation in the last few years. Recent progress in various plasticity modulation techniques has pushed the research of synaptic electronics from static plasticity simulation to dynamic plasticity modulation, improving the accuracy of neuromorphic computing and providing strategies for implementing neuromorphic sensing functions. Herein, several fascinating strategies for synaptic plasticity modulation through chemical techniques, device structure design, and physical signal sensing are reviewed. For chemical techniques, the underlying mechanisms for the modification of functional materials were clarified and its effect on the expression of synaptic plasticity was also highlighted. Based on device structure design, the reconfigurable operation of neuromorphic devices was well demonstrated to achieve programmable neuromorphic functions. Besides, integrating the sensory units with neuromorphic processing circuits paved a new way to achieve human-like intelligent perception under the modulation of physical signals such as light, strain, and temperature. Finally, considering that the relevant technology is still in the basic exploration stage, some prospects or development suggestions are put forward to promote the development of neuromorphic devices.

Fenton reaction in the process of "Laser + Fe" mode excited plasma for Rhodamine B degradation.

The spectral emission of laser-induced plasma in water has a broadband continuum containing ultraviolet light, which can be used as a novel light source for the degradation of organic compounds. We studied the degradation process of the organic dye Rhodamine B (RhB) using plasma light source excited by the "Laser + Fe" mode. Spectral analysis and reaction kinetics modelling were used to study the degradation mechanism. The degradation process using this light source could be divided into two stages. The initial stage was mainly photocatalytic degradation, where ultraviolet light broke the chemical bond of RhB, and then RhB was degraded by the strong oxidising ability of ·OH. As the iron and hydrogen ion concentrations increased, the synergistic effect of photocatalysis and the Fenton reaction further enhanced the degradation rate in the later stage. The plasma excited by the "Laser + Fe" mode achieved photodegradation by effectively enhancing the ultraviolet wavelength ratio of the emission spectrum and triggered the Fenton reaction to achieve rapid organic matter degradation. Our findings indicate that the participation of the Fenton reaction can increase the degradation rate by approximately 10 times. Besides, the impact of pH on degradation efficiency demonstrates that both acidic and alkaline environments have better degradation effects than neutral conditions; this is because acidic environments can enhance the Fenton reaction, while alkaline environments can provide more ·OH.

Association between intracellular adenosine triphosphate content of CD4+ T lymphocytes and mortality in sepsis patients: A prospective observational study.

OBJECTIVE: This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. METHODS: 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. RESULTS: Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. CONCLUSIONS: Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.

Comparison of physicochemical parameters, microbial community composition and flavor substances during mechanical and traditional brewing process of Jiang-flavor baijiu.

Mechanized, automated and intelligent brewing is an important trend of innovation and transition in Jiang-flavor baijiu industry. In this study, physicochemical parameters, microbial community composition and flavor substances during 3rd round heap fermentation between mechanical and traditional workshop were investigated and compared based on traditional culturable methods, high-throughput sequencing technology and gas chromatography analysis. The dominant bacterial and fungal genera were consistent between the two workshops, but mechanized brewing had a significant impact on the composition of fungal communities. Rhodococcus and Monascus were special genera in mechanical workshop. The interaction relationship between physicochemical parameters and dominant microorganisms in mechanized workshop was different from traditional workshop as well. This study provided a scientific basis for further analyzing the mechanism of mechanized brewing of Jiang-flavor baijiu. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01483-y.

A multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma.

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.

Transcriptome Analysis Reveals Dynamic Microglial-Induced A1 Astrocyte Reactivity via C3/C3aR/NF-κB Signaling After Ischemic Stroke.

Microglia and astrocytes are key players in neuroinflammation and ischemic stroke. A1 astrocytes are a subtype of astrocytes that are extremely neurotoxic and quickly kill neurons. Although the detrimental A1 astrocytes are present in many neurodegenerative diseases and are considered to accelerate neurodegeneration, their role in the pathophysiology of ischemic stroke is poorly understood. Here, we combined RNA-seq, molecular and immunological techniques, and behavioral tests to investigate the role of A1 astrocytes in the pathophysiology of ischemic stroke. We found that astrocyte phenotypes change from a beneficial A2 type in the acute phase to a detrimental A1 type in the chronic phase following ischemic stroke. The activated microglial IL1α, TNF, and C1q prompt commitment of A1 astrocytes. Inhibition of A1 astrocytes induction attenuates reactive gliosis and ameliorates morphological and functional defects following ischemic stroke. The crosstalk between astrocytic C3 and microglial C3aR contributes to the formation of A1 astrocytes and morphological and functional defects. In addition, NF-κB is activated following ischemic stroke and governs the formation of A1 astrocytes via direct targeting of inflammatory cytokines and chemokines. Taken together, we discovered that A2 astrocytes and A1 astrocytes are enriched in the acute and chronic phases of ischemic stroke respectively, and that the C3/C3aR/NF-κB signaling leads to A1 astrocytes induction. Therefore, the C3/C3aR/NF-κB signaling is a novel therapeutic target for ischemic stroke treatment.

Collagen XVII promotes dormancy of colorectal cancer cells by activating mTORC2 signaling.

Tumor dormancy is the underpinning for cancer relapse and chemoresistance, leading to massive cancer-related death in colorectal cancer (CRC). However, our comprehension of the mechanisms dictating tumor dormancy and strategies for eliminating dormant tumor cells remains restricted. In this study, we identified that collagen XVII (COL17A1), a hemidesmosomal transmembrane protein, can promote the dormancy of CRC cells. The upregulation of COL17A1 was observed to prolong quiescence periods and diminish drug susceptibility of CRC cells. Mechanistically, COL17A1 acts as a scaffold, enhancing the crosstalk between mTORC2 and Akt, thereby instigating the mTORC2-mediated dormant signaling. Notably, the activation of mTORC2 is contingent upon the intracellular domain of COL17A1, regardless of its ectodomain shedding. Our findings underscore a pivotal role of the COL17A1-mTORC2 axis in CRC dormancy, suggesting that mTORC2-specific inhibitors may hold therapeutic prospects for the eradication of dormant tumor cells.

Cultural landscape resilience evaluation of Great Wall Villages: A case study of three villages in Chicheng County.

The Great Wall Villages (GWVs) are linked to the Great Wall in history, culture, and ecology. The cultural landscape resilience of Great Wall Villages (CLRGWVs) is distinctly significant. However, it is influenced by urbanization, pollution, and a lack of awareness of cultural landscape protection. Therefore, conservation and development practices still lack scientific strategies and guidance. This study proposes a new assessment system to quantify CLRGWVs, an analysis of the main influencing factors of resilience, and optimization paths to maintain sustainable development. Based on the socio-ecological system, this research designed the assessment with three criteria, eleven factors, and thirty-three indexes from the perspective of CLRGWVs. Furthermore, a demonstration test was constructed in Ningyuanbao Village, Dushikou Village, and Longmensuo Village in Chicheng County, Hebei Province, China. The results showed that there is some disparity between the three GWVs, with the resilience score of Dushikou Village being the highest in terms of resistance and learning. In contrast, Ningyuanbao Village's resilience score is the lowest since resistance, recovery, and learning capacity are lower than in Dushikou and Longmensuo. Some influencing factors were found to be highly related to adaptive capacity. Lastly, some low-resilience aspects were identified as critical improvement targets for which corresponding optimization strategies should be proposed. This could be applied to streamline resilience optimization paths according to local conditions. This paper provides new ideas and directions for dealing with the sustainable development of villages and the conservation of cultural landscapes. It will also help villages deal with the relationship between socio-economic development and the conservation of cultural landscapes.

Dissecting caspase-2-mediated cell death: from intrinsic PIDDosome activation to chemical modulation.

Caspase-2, a highly conserved member of the caspase family, is considered an initiator caspase that triggers apoptosis in response to some cellular stresses. Previous studies suggest that an intracellular multi-protein complex PIDDosome, induced by genotoxic stress, serves as a platform for caspase-2 activation. However, due to caspase-2's inability to process effector caspases, the mechanism underlying caspase-2-mediated cell death upon PIDDosome activation remains unclear. Here we conducted an unbiased genome-wide genetic screen and identified that the Bcl2 family protein BID is required for PIDDosome-induced, caspase-2-mediated apoptosis. PIDDosome-activated caspase-2 directly and functionally processes BID to signal the mitochondrial pathway for apoptosis induction. Additionally, a designed chemical screen identified a compound, HUHS015, that specifically activates caspase-2-mediated apoptosis. HUHS015-stimulated apoptosis also requires BID but is independent of the PIDDosome. Through extensive structure-activity relationship efforts, we identified a derivative with a potency of ~ 60 nmol/L in activating caspase-2-mediated apoptosis. The HUHS015-series of compounds act as efficient agonists that directly target the interdomain linker in caspase-2, representing a new mode of initiator caspase activation. Human and mouse caspase-2 differ in two crucial residues in the linker, rendering a selectivity of the agonists for human caspase-2. The caspase-2 agonists are valuable tools to explore the physiological roles of caspase-2-mediated cell death and a base for developing small-molecule drugs for relevant diseases.

Analysis of factors influencing fall risk among elderly people in rural of China.

Falls can cause serious health problems in the elderly. China is gradually entering a moderately aging society. In rural areas of China, the elderly are at a higher risk of falling. This study aims to explore and analyze the factors affecting the fall risk of elderly people in rural areas of China, and provide theoretical basis for reducing the fall risk of elderly people. M County, Anhui Province, China was selected as the survey site by the typical field sampling method, and the elderly people in rural areas were selected as the research objects. A total of 1187 people were investigated. Mann-Whitney U test and Kruskal-Wallis H test were used for univariate analysis, and multiple linear regression was used for multivariate analysis. Chronic diseases, multimorbidity, daily living ability, mental health, working status and family doctors are the factors that influence falls among elderly people in rural areas of China (P < 0.05, Adjusted R2 = 0.395). The falls risk of the elderly in rural areas of China is influenced by multiple factors. Therefore, comprehensive measures should be taken to reduce the fall risk by comprehensively evaluating the influencing factors.

Contezolid-Containing Regimen Successfully Treated Multiple Drug Resistance Mycobacterium Abscessus Complex Infection of Skin: A Case Report and Literature Review.

Background: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited. Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to "beauty needle" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with "metronidazole", and oral "cephalosporin" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient's facial symptoms were significantly improved, and no drug-related adverse reactions happened. Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers.

BACKGROUND: Portal vein thrombosis (PVT), a complication of liver cirrhosis, is a major public health concern. PVT prediction is the most effective method for PVT diagnosis and treatment. AIM: To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis. METHODS: Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved. Following a 1:1 propensity score matching 572 patients with cirrhosis were screened, and relevant clinical data were collected. PVT risk factors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis. Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables. A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT, and its predictive performance was verified using a receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA). Finally, a network calculator was constructed based on the nomograms. RESULTS: This study enrolled 286 cirrhosis patients with PVT and 286 without PVT. LASSO analysis revealed 13 variables as strongly associated with PVT occurrence. Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors, including etiology, ascites, gastroesophageal varices, platelet count, D-dimer, portal vein diameter, portal vein velocity, aspartate transaminase to neutrophil ratio index, and platelet-to-lymphocyte ratio. LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables. A nomogram was constructed based on the screened independent risk factors. The nomogram had excellent predictive performance, with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups, respectively. Calibration curves and DCA revealed its good clinical performance. Finally, the optimal cutoff value for the total nomogram score was 0.513. The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706, respectively. CONCLUSION: A nomogram for predicting PVT occurrence was successfully developed and validated, and a network calculator was constructed. This can enable clinicians to rapidly and easily identify high PVT risk groups.

Image restoration for ring-array photoacoustic tomography system based on blind spatially rotational deconvolution.

Ring-array photoacoustic tomography (PAT) system has been widely used in noninvasive biomedical imaging. However, the reconstructed image usually suffers from spatially rotational blur and streak artifacts due to the non-ideal imaging conditions. To improve the reconstructed image towards higher quality, we propose a concept of spatially rotational convolution to formulate the image blur process, then we build a regularized restoration problem model accordingly and design an alternating minimization algorithm which is called blind spatially rotational deconvolution to achieve the restored image. Besides, we also present an image preprocessing method based on the proposed algorithm to remove the streak artifacts. We take experiments on phantoms and in vivo biological tissues for evaluation, the results show that our approach can significantly enhance the resolution of the image obtained from ring-array PAT system and remove the streak artifacts effectively.

Circ_0001786 facilitates gefitinib resistance and malignant progression in non-small cell lung cancer via miR-34b-5p/SRSF1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a widespread cancer and gefitinib is a primary therapy for NSCLC patients. Nevertheless, the underlying mechanisms for the progression of acquired drug resistance have not been clarified. The aim of this study was to investigate the role of circular RNA (circ_0001786) in gefitinib-resistant NSCLC. METHODS: Firstly, the expression of circ_0001786, miR-34b-5p and SRSF1 were assayed using qRT-PCR. Subsequently, CCK-8 test was utilized to measure the semi-inhibitory concentration (IC50) of cellular gefitinib. Apoptosis was identified by flow cytometry. At last, dual luciferase assay was applied to prove the binding association between miR-34b-5p, circ_0001786 or SRSF1. RESULTS: Our research disclosed that circ_0001786 was heightened in gefitinib-resistant NSCLC cells and tissues. Knockdown of circ_0001786 restrained IC50 values of gefitinib, attenuated the clonogenic ability and facilitated apoptosis in HCC827-GR and PC9-GR. In addition, circ_0001786 was a molecular sponge for miR-34b-5p. Silencing miR-34b-5p rescued the inhibitory impact of circ_0001786 knockdown on IC50 and cell cloning ability. Moreover, miR-34b-5p directly targeted SRSF1. Importantly, circ_0001786 enhanced gefitinib tolerance and malignant development in NSCLC through miR-34b-5p/SRSF1 pathway. CONCLUSION: This research revealed a novel mechanism by which circ_0001786 enhanced NSCLC resistance to gefitinib by sponging miR-34b-5p and upregulating SRSF1. circ_0001786 was a potential target for improving the treatment of gefitinib-resistant NSCLC patients.

Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.