A novel endocardial activation-derived predictor for focal paraseptal atrial tachycardias: Evidence from a multicenter cohort study.

BACKGROUND: The electrocardiogram-based algorithm for predicting paraseptal atrial tachycardia (PSAT) is limited by the significant overlaps in P-wave morphology originating from various paraseptal sites. OBJECTIVES: The goals of this study were to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation-derived predictor for the ablation site. METHODS: Forty-four patients (11 men; mean age 62.6 ± 14.7 years) with PSAT ablation in 4 tertiary medical centers were assigned to 3 groups according to the ablation site: right atrial (RA) para-Hisian region (group 1, n = 10), noncoronary cusp (NCC) (group 2, n = 13), and left atrial (LA) paraseptal area (group 3, n = 21). Multiple-chamber activation mapping was performed guided by a 3-dimensional navigation system. The discrepancies in the earliest activation time between 2 of 3 chambers (ΔRA-LA, ΔRA-NCC, and ΔLA-NCC) were calculated in each group and used for pairwise comparisons. RESULTS: There was a significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC among the 3 groups. ΔRA-LA was the only parameter that could consistently predict the ablation site of PSAT with good accuracy (area under the curve 1.000, sensitivity 100% and specificity 100%, and cutoff value 7 ms for predicting right para-Hisian or NCC ablation; area under the curve 0.974, sensitivity 92.3% and specificity 95.2%, and cutoff value -4 ms for predicting NCC or left paraseptal ablation). Based on 2 cutoff values, a 2-step algorithm was developed to predict the ablation site of PSAT with a positive predictive value of 95.4% and a negative predictive value of 97.0%. CONCLUSION: ΔRA-LA is a useful endocardial activation-derived parameter for predicting the successful ablation site of PSAT.

C-H Bond Sulfonylation from Thianthrenium Salts and DABCO·(SO2)2: Synthesis of 2-Sulfonylindoles.

A three-component reaction of 1-(1H-indol-1-yl)isoquinolines or 1-(pyridin-2-yl)-1H-indoles, DABCO·(SO2)2, and thianthrenium salts under synergistic photoredox and palladium catalysis is accomplished. This direct C-H bond sulfonylation of indoles with the insertion of sulfur dioxide under mild conditions works efficiently, giving rise to a wide range of 2-sulfonated indoles in moderate to good yields under mild conditions. In this protocol, the generality of aryl/alkyl thianthrenium salts is demonstrated as well. A photoredox radical process combined with palladium catalysis is proposed.

The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Reducing Indoor Particulate Air Pollution Improves Student Test Scores: A Randomized Double-Blind Crossover Study.

Short-term exposure to air pollution is associated with a decline in cognitive function. Standardized test scores have been employed to evaluate the effects of air pollution exposure on cognitive performance. Few studies aimed to prove whether air pollution is responsible for reduced test scores; none have implemented a "gold-standard" method for assessing the association such as a randomized, double-blind intervention. This study used a "gold-standard" method─randomized, double-blind crossover─to assess whether reducing short-term indoor particle concentrations results in improved test scores in college students in Tianjin, China. Participants (n = 162) were randomly assigned to one of two similar classrooms and completed a standardized English test on two consecutive weekends. Air purifiers with active or sham (i.e., filter removed) particle filtration were placed in each classroom. The filtration mode was switched between the two test days. Linear mixed-effect models were used to evaluate the effect of the intervention mode on the test scores. The results show that air purification (i.e., reducing PM) was significantly associated with increases in the z score for combined (0.11 [95%CI: 0.02, 0.21]) and reading (0.11 [95%CI: 0.00, 0.22]) components. In conclusion, a short-term reduction in indoor particle concentration led to improved test scores in students, suggesting an improvement in cognitive function.

Robust Thermal Transport across the Surface-Active Bonding SiC-on-SiC.

Surface-active bonding (SAB) is a promising technique for semiconductors directly bonding. However, the interlayer of the bonding interface and the reduced layer thickness may affect thermal transport. In this study, the temperature-dependent cross-plane thermal conductivity of 4H-SiC thin films and the effective thermal boundary resistance (TBReff) of the bonding SiC-on-SiC are measured by the multiple-probe wavelength nanosecond transient thermoreflectance (MW-TTR). The measured temperature-dependent cross-plane thermal conductivity of the 4H-SiC thin film exhibits good quantitative agreement with calculation by density functional theory (DFT) including higher-order four-phonon (4ph) scattering, especially at high temperatures (>400 K). The theoretical calculations indicate the non-negligible importance of 4ph scattering in 4H-SiC high-temperature applications, due to the significantly increasing 4ph scattering rate at increasing temperature and strong temperature dependence of 4ph scattering. The measured nonzero but small TBReff (2.33 + 0.43/-1.15 m2 K/GW) at the SiC-SiC interface is analyzed with molecular dynamics (MD) simulation, indicating that a strong bonding interface with an extremely thin interlayer is formed by the SAB process. Two-dimensional finite element simulations of the experimental equivalent structures are further investigated, and the significant effects (at least 19 °C) of TBReff on the maximum temperature (Tmax) are confirmed. This study provides insight into the fundamental phonon transport and interface thermal transport mechanism in SAB SiC-on-SiC and paves the way for improved 4H-SiC efficient device manufacturing and thermal management.

Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

Investigating the effects of Laggera pterodonta on H3N2-Induced inflammatory and immune responses through network pharmacology, molecular docking, and experimental validation in a mice model.

For centuries, Laggera pterodonta (LP), a Chinese herbal medicine, has been widely employed for treating respiratory infectious diseases; however, the mechanism underlying LP's effectiveness against the influenza A/Aichi/2/1968 virus (H3N2) remains elusive. This study aims to shed light on the mechanism by which LP combats influenza in H3N2-infected mice. First, we conducted quasi-targeted metabolomics analysis using liquid chromatography-mass spectrometry to identify LP components. Subsequently, network pharmacology, molecular docking, and simulation were conducted to screen candidate targets associated with AKT and NF-κB. In addition, we conducted a series of experiments including qPCR, hematoxylin-eosin staining, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay to provide evidence that LP treatment in H3N2-infected mice can reduce pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß, and MCP-1) while increasing T cells (CD3+, CD4+, and CD8+) and syndecan-1 and secretory IgA expression. This, in turn, aids in the prevention of excessive inflammation and the fortification of immunity, both of which are compromised by H3N2. Finally, we utilized a Western blot assay to confirm that LP indeed inhibits the AKT/NF-κB signaling cascade. Thus, the efficacy of LP serves as a cornerstone in establishing a theoretical foundation for influenza treatment.

Texture analysis of apparent diffusion coefficient maps: can it identify nonresponse to neoadjuvant chemotherapy for additional radiation therapy in rectal cancer patients?

Background: Neoadjuvant chemotherapy (NCT) alone can achieve comparable treatment outcomes to chemoradiotherapy in locally advanced rectal cancer (LARC) patients. This study aimed to investigate the value of texture analysis (TA) in apparent diffusion coefficient (ADC) maps for identifying non-responders to NCT. Methods: This retrospective study included patients with LARC after NCT, and they were categorized into nonresponse group (pTRG 3) and response group (pTRG 0-2) based on pathological tumor regression grade (pTRG). Predictive texture features were extracted from pre- and post-treatment ADC maps to construct a TA model using RandomForest. The ADC model was developed by manually measuring pre- and post-treatment ADC values and calculating their changes. Simultaneously, subjective evaluations based on magnetic resonance imaging assessment of TRG were performed by two experienced radiologists. Model performance was compared using the area under the curve (AUC) and DeLong test. Results: A total of 299 patients from two centers were divided into three cohorts: the primary cohort (center A; n = 194, with 36 non-responders and 158 responders), the internal validation cohort (center A; n = 49, with 9 non-responders) and external validation cohort (center B; n = 56, with 33 non-responders). The TA model was constructed by post_mean, mean_change, post_skewness, post_entropy, and entropy_change, which outperformed both the ADC model and subjective evaluations with an impressive AUC of 0.997 (95% confidence interval [CI], 0.975-1.000) in the primary cohort. Robust performances were observed in internal and external validation cohorts, with AUCs of 0.919 (95% CI, 0.805-0.978) and 0.938 (95% CI, 0.840-0.985), respectively. Conclusions: The TA model has the potential to serve as an imaging biomarker for identifying nonresponse to NCT in LARC patients, providing a valuable reference for these patients considering additional radiation therapy.

Hydrodynamic cultivation of aeration-free oxygenic photogranules is favored by sufficient amounts of organic carbon.

Oxygenic photogranules (OPGs) have great potential for the aeration-free treatment of various wastewater, however, the effects of wastewater carbon composition on OPGs remain unknown. This study investigated the hydrodynamic photogranulation in three types of wastewater with the same total carbon concentration but different inorganic/organic carbon compositions, each operated at two replicated reactors. Results showed that photogranulation failed in reactors fed with only inorganic carbon. In reactors with equal inorganic and organic carbon, loose-structured OPGs formed but then disintegrated. Comparatively, reactors treating organic carbon-based wastewater obtained regular and dense OPGs with better settleability, lower effluent turbidity, excellent structural stability, and higher carbon assimilation rate. Sufficient amounts of organic carbon were crucial for the formation and stability of OPGs as they promoted the secretion of extracellular polymeric substances (EPS) and the growth of filamentous cyanobacteria. This study provides a basis for the startup of OPGs process and facilitates its large-scale application.

Beyond feast and famine: Cultivating hydrodynamic oxygenic photogranules with better performances under permanent feast regime.

Oxygenic photogranules (OPGs) are currently obtained in permanent famine or cyclic feast-famine regimes. Whether photogranulation occurs under a permanent feast regime and how these regimes impact OPGs are unknown. Herein, the three regimes, each applied in two replicate hydrodynamic reactors, were established by different feeding frequencies. Results showed that OPGs were successfully cultivated in all regimes after 24-36 days of photogranulation phases with similar microbial community functions, including filamentous gliding, extracellular polymeric substances production, and carbon/nitrogen metabolism. The OPGs were then operated under the same sequencing batch mode and all achieved efficient removal of chemical oxygen demand (>91 %), ammonium (>96 %), and total nitrogen (>76 %) after different adaptation periods (19-41 days). Notably, the permanent feast regime obtained OPGs with the best physicochemical properties, the shortest adaptation period, and the lowest effluent turbidity, thus representing a novel means of hydrodynamic cultivating OPGs with better performances for sustainable wastewater treatment.

Anaerobic acidification membrane bioreactor operating at acidic condition for treating concentrated municipal wastewater: Performance and implication.

To address the low-carbon treatment requirements for municipal wastewater, a novel anaerobic acidification membrane bioreactor (AAMBR) was developed for recovering organic matter in terms of volatile fatty acids (VFAs). While the AAMBR successfully generated VFAs from municipal wastewater through forward osmosis (FO) membrane concentration, its operation was limited to a single pH value of 10.0. Here, performance of the AAMBR operating at acidic condition was evaluated and compared with that at alkaline condition. The findings revealed that the AAMBR with pH 5.0 efficiently transformed organic matter into acetic acid, propionic acid, and butyric acid, resulting in a VFAs yield of 0.48 g/g-CODfeed. In comparison with the AAMBR at pH 10.0, this study achieved a similar VFAs yield, a lower fouling tendency, a lower loss of nutrients and a lower controlling cost. In conclusion, this study demonstrated that a pH of 5.0 is optimal for the AAMBR treating municipal wastewater.

Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of Denglao Qingguan decoction against HCoV-229E.

Background: Denglao Qingguan decoction (DLQGD) has been extensively utilized for the treatment of colds, demonstrating significant therapeutic efficacy. Human Coronavirus 229E (HCoV-229E) is considered a crucial etiological agent of influenza. However, the specific impact and underlying mechanisms of DLQGD on HCoV-229E remain poorly understood. Methods: Active ingredients and targets information of DLQGD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, and Swiss ADEM database. The Genecard database was used to collect HCoV-229E related targets. We built an "ingredient-target network" through Cytoscape. Protein - Protein interaction (PPI) networks were mapped using the String database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were enriched using the DAVID database. Then, we used molecular docking techniques to verify the binding activity between the core compounds and the core gene targets. Finally, in vitro experiments were conducted to validate DLQGD's antiviral activity against HCoV-229E and assess its anti-inflammatory effects. Results: In total, we identified 227 active components in DLQGD. 18 key targets involved in its activity against HCoV-229E. Notably, the core active ingredients including quercetin, luteolin, kaempferol, ß-sitosterol, and apigenin, and the core therapeutic targets were CXCL8, RELA, MAPK14, NFKB1, and CXCL10, all associated with HCoV-229E. KEGG enrichment results included IL-17 signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and so on. The core active ingredients and the core therapeutic targets and Human Aminopeptidase N (ANPEP) all showed good binding activity by molecular docking verification. In vitro, DLQGD exhibited anti-HCoV-229E activity and anti-inflammatory effects. Conclusion: Our study suggests that DLQGD has both effects of anti-HCoV-229E and anti-inflammatory. The core active ingredients (quercetin, luteolin, kaempferol, ß-sitosterol, apigenin) and the core therapeutic targets (CXCL8, RELA, MAPK14, NFKB1, CXCL10) may play key roles in the pharmacological action of DLQGD against HCoV-229E.

The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma.

Pruritus of lymphoma is commonly associated with both Hodgkin lymphoma (HL) and angioimmunoblastic T cell lymphoma (AITL) and critically affects the life quality of patient. Recent evidence suggests that the pruritogenic cytokines seem to play a significant role in the genesis of chronic. This study aims to investigate the cytokines associated with itching in lymphoma patients and provide the basis for potential therapeutic targets. Serum samples were collected from 60 lymphoma patients, including 47 with Hodgkin lymphoma (HL) and 13 with angioimmunoblastic T-cell lymphoma (AITL), serving as the observation group (lymphoma group, LP group, n = 60). Additionally, serum samples from 8 healthy donors (HD group, n = 8) were collected for comparison. Within the lymphoma group, patients were stratified into those with pruritus (LWP group, n = 30) and those without pruritus (LWOP group, n = 30) based on the presence of skin pruritus symptoms. Elevated levels of multiple cytokines were significantly observed in the LP group in comparison to the HD group (p < 0.01). Patients in LWP group exhibited higher serum levels of IL-31 (p < 0.001), IL-1ß (P = 0.039), and IL-1α (P = 0.037) compared to LWOP group. Notably, serum IL-31 levels were higher in advanced AITL patients (stage IV) than in early AITL patients (stage I-Ⅲ, P < 0.05). In subgroup analysis, patients with pruritus in the AITL group exhibited higher serum levels of MIG and CTACK compared to HL group, whereas PDGF-BB levels were significantly lower (p < 0.05). Elevated serum levels of IL-31, IL-1ß, and IL-1α are linked to lymphoma-associated pruritus. Differences in serum cytokine profiles between HL and AITL subgroups are also highlighted. These findings offer valuable insights for clinical intervention in managing lymphoma-related pruritus.

New insights on destruction mechanisms of waste activated sludge during simultaneous thickening and digestion process via forward osmosis membrane.

This study delved into the efficacy of sludge digestion and the mechanisms involved in sludge destruction during the implementation of forward osmosis process for sludge thickening and digestion (FO-MSTD). Utilizing a lab-scale FO membrane reactor for the thickening and digestion of waste activated sludge (WAS), the investigation explored the effects of sludge thickening and digestion in FO-MSTD processes using draw solutions of varying concentrations. The findings underscored the significance of hydraulic retention time (HRT) as a pivotal parameter influencing the swift thickening or profound digestion of sludge. Consequently, tailoring the HRT to specific processing objectives emerged as a key strategy for achieving desired treatment outcomes. In the investigation, the use of a 1 M NaCl draw solution in the FO-MSTD process showcased enhanced thickening and digestion capabilities. This specific setup raised the concentration of mixed liquor suspended solids (MLSS) to over 30 g/L and achieved a 42.7% digestion efficiency of mixed liquor volatile suspended solids (MLVSS) within an operational timeframe of 18 days. Furthermore, the research unveiled distinct stages in the sludge digestion process of the FO-MSTD system, characterized by fully aerobic digestion and aerobic-local anaerobic co-existing digestion. In the fully aerobic digestion stage, the sludge digestion rate exhibited a steady increase, leading to the breakdown of sludge floc structures and the release of a substantial amount of nutrients into the sludge supernatant. The predominant microorganisms during this stage were typical functional microorganisms found in wastewater treatment systems. Transitioning into the aerobic-local anaerobic co-existing digestion stage, both MLSS concentration and MLVSS digestion efficiency continued to rise, accompanied by a decreasing dissolved oxygen (DO) concentration. More organic matter was released into the supernatant, and sludge microbial flocs tended to reaggregate. The localized anaerobic environment within the FO-MSTD reactor fostered an increase in the relative abundance of bacteria with nitrogen and phosphorus removal functions, thereby positively impacting the mitigation of total nitrogen (TN) and total phosphorus (TP) concentrations in the sludge supernatant. The results of this research enhance comprehension of the advanced FO-MSTD technology in the treatment of WAS.

Robust positive association between serum urate and the risk of chronic obstructive pulmonary disease: hospital-based cohort and Mendelian randomisation study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and hyperuricaemia are both characterised by systemic inflammation. Preventing chronic diseases among the population with common metabolic abnormality is an effective strategy. However, the association of hyperuricaemia with the higher incidence and risk of COPD remains controversial. Therefore, replicated researches in populations with distinct characteristics or demographics are compellingly warranted. METHODS: This cohort study adopted a design of ambispective hospital-based cohort. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to minimise the effects of potential confounding factors. A Cox regression model and restricted cubic spline (RCS) model were applied further to assess the effect of serum urate on the risk of developing COPD. Finally, we conducted a two-sample Mendelian randomisation (MR) analysis to explore evidence of causal association. RESULTS: There is a higher incidence in the population with hyperuricaemia compared with the population with normal serum urate (22.29/1000 person-years vs 8.89/1000 person-years, p=0.009). This result is robust after performing PSM (p=0.013) and IPTW (p<0.001). The Cox model confirms that hyperuricaemia is associated with higher risk of developing COPD (adjusted HR=3.35 and 95% CI=1.61 to 6.96). Moreover, RCS shows that the risk of developing COPD rapidly increases with the concentration of serum urate when it is higher than the reference (420 µmol/L). Finally, in MR analysis, the inverse variance weighted method evidences that a significant causal effect of serum urate on COPD (OR=1.153, 95% CI=1.034 to 1.289) is likely to be true. The finding of MR is robust in the repeated analysis using different methods and sensitivity analysis. CONCLUSIONS: Our study provides convincing evidence suggesting a robust positive association between serum urate and the risk of developing COPD, and indicates that the population with hyperuricaemia is at high risk of COPD in the Chinese population who seek medical advice or treatment in the hospital.

Characterization of tomato autophagy-related SlCOST family genes.

Autophagy is a eukaryote-specific cellular process that can engulf unwanted targets with double-membrane autophagosomes and subject them to the vacuole or lysosome for breaking down and recycling, playing dual roles in plant growth and environmental adaptions. However, perception of specific environmental signals for autophagy induction is largely unknown, limiting its application in agricultural usage. Identification of plant-unique DUF641 family COST1 (Constitutively Stressed 1) protein directly links drought perception and autophagy induction, shedding light on manipulating autophagy for breeding stress tolerant crops. In this study, we performed a genome-wide analysis of DUF641/COST family in tomato, and identified five SlCOST genes SlCOST1, -2, -3, -4, and -5. SlCOST genes show both overlapping and distinct expression patterns in plant growth and stress responding. In addition, SlCOST1, -3, -4, -5 proteins demonstrate co-localization with autophagy adaptor protein ATG8e, and all five SlCOST proteins show interactions ATG8e in planta. However, only SlCOST1, the closest ortholog of Arabidopsis AtCOST1, can restore cost1 mutant to WT level, suggesting conserved role of COST1 and functional diversification of SlCOST family in tomato. Our study provides clues for future investigation of autophagy-related COST family and its promising implementations in breeding crops with robust environmental plasticity.

Mechanism of Action of the Plateau-Adapted Gene PPARA in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex respiratory disorder influenced by various factors and involving multiple genes. Respiratory dysfunction in COPD patients leads to hypoxia, resulting in limited oxygen uptake. Peroxisome proliferator-activated receptor alpha (PPARA) is a plateau-adapted gene that regulates respiratory function in populations adapted to high-altitude areas through multiple pathways. Interestingly, PPARA expression is higher in long-term inhabiting Tibetan populations that have adapted to the plateau environment. However, in patients with COPD, the expression of PPARA is downregulated, leading to dysregulation of the hypoxia-inducible factor pathway. Moreover, abnormal PPARA expression in lung epithelial cells triggers inflammatory responses, oxidative stress, and disrupted lipid metabolism, thereby exacerbating disease progression. Thus, this paper explored the mechanism underlying the role of plateau-adapted PPARA in COPD, providing essential theoretical insights into the treatment and prevention of COPD in high-altitude regions.

GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism. Methods: Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD. Results: The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05). Conclusion: In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.