The CRL3KCTD10 ubiquitin ligase-USP18 axis coordinately regulates cystine uptake and ferroptosis by modulating SLC7A11.

SLC7A11 is a cystine transporter and ferroptosis inhibitor. How the stability of SLC7A11 is coordinately regulated in response to environmental cystine by which E3 ligase and deubiquitylase (DUB) remains elusive. Here, we report that neddylation inhibitor MLN4924 increases cystine uptake by causing SLC7A11 accumulation, via inactivating Cullin-RING ligase-3 (CRL-3). We identified KCTD10 as the substrate-recognizing subunit of CRL-3 for SLC7A11 ubiquitylation, and USP18 as SLC7A11 deubiquitylase. Upon cystine deprivation, the protein levels of KCTD10 or USP18 are decreased or increased, respectively, contributing to SLC7A11 accumulation. By destabilizing or stabilizing SLC7A11, KCTD10, or USP18 inversely regulates the cystine uptake and ferroptosis. Biologically, MLN4924 combination with SLC7A11 inhibitor Imidazole Ketone Erastin (IKE) enhanced suppression of tumor growth. In human breast tumor tissues, SLC7A11 levels were negatively or positively correlated with KCTD10 or USP18, respectively. Collectively, our study defines how SLC7A11 and ferroptosis is coordinately regulated by the CRL3KCTD10/E3-USP18/DUB axis, and provides a sound rationale of drug combination to enhance anticancer efficacy.

Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

What influences the close contact between health care workers and patients? An observational study in a hospital dental outpatient department.

BACKGROUND: Dental outpatient departments, characterized by close proximity and unmasked patients, present a considerable risk of respiratory infections for health care workers (HCWs). However, the lack of comprehensive data on close contact (<1.5m) between HCWs and patients poses a significant obstacle to the development of targeted control strategies. METHODS: An observation study was conducted at a hospital in Shenzhen, China, utilizing depth cameras with machine learning to capture close-contact behaviors of patients with HCWs. Additionally, questionnaires were administered to collect patient demographics. RESULTS: The study included 200 patients, 10 dental practitioners, and 10 nurses. Patients had significantly higher close-contact rates with dental practitioners (97.5%) compared with nurses (72.8%, P < .001). The reason for the visit significantly influenced patient-practitioner (P = .018) and patient-nurse (P = .007) close-contact time, with the highest values observed in prosthodontics and orthodontics patients. Furthermore, patient age also significantly impacted the close-contact rate with nurses (P = .024), with the highest rate observed in patients below 14 years old at 85% [interquartile range: 70-93]. CONCLUSIONS: Dental outpatient departments exhibit high HCW-patient close-contact rates, influenced by visit purpose and patient age. Enhanced infection control measures are warranted, particularly for prosthodontics and orthodontics patients or those below 14 years old.

[Spatio-temporal Evolution and Driving Factors of Ecological Environment Quality in the Huaihe River Basin Based on RSEI].

Clarifying the spatio-temporal evolution of the ecological environment quality of a watershed and its response to the natural environment and human factors are crucial for policy implementation in the ecological environment of the watershed. Using the Google earth engine（GEE） to establish a remote sensing ecological index （RSEI）, the spatio-temporal changes in the ecological environment quality of the Huaihe River Basin from 2002 to 2022 were evaluated combined with trend analysis, variation coefficient, and Hurst index. The main driving factors of spatial differentiation of RSEI were explored using the geographic detector. The results showed that： ① In the past 21 years, RSEI of the Huaihe River Basin had generally improved, but it showed a gradual upward-downward trend. Overall, the area of poor and less poor grades decreased, the area of medium grades increased, and the area of good and excellent grades increased. The improved area accounted for 55.93%, and the degraded area accounted for 22.01%. ② In terms of spatial distribution, RSEI gradually deteriorated from east to west （except in the northwest and southwest marginal mountainous areas）. The stability was better in the east and worse in the western and central areas. In the future, the ecological quality change in the basin was prone to be anti-sustainable and mainly improved. ③ Factor detection results showed that the spatial differentiation of RSEI in the basin was mainly driven by vegetation factors, followed by altitude. The interaction between two factors enhanced the driving force for RSEI spatial differentiation, in which the interaction between vegetation factor and elevation had the strongest driving force for RSEI spatial differentiation, reaching 86.3%.

The size-dependence and reversibility of polystyrene nanoplastics-induced hepatic pyroptosis in mice through TXNIP/NLRP3/GSDMD pathway.

As emerging environmental contaminants, nanoplastics (NPs) are progressively accumulating in terrestrial and aquatic ecosystems worldwide, posing a potential threat to human health. The liver is considered as one of the primary organs targeted by NPs accumulation in living organisms. However, there remains a large knowledge gap concerning NPs-induced hepatotoxicity. In this study, we examined the impact of chronic exposure to environmentally relevant doses of polystyrene (PS) NPs on hepatic pyroptosis in mice. The results demonstrated that both particle sizes of PS-NPs (100 nm and 500 nm) significantly triggered pyroptosis in the mouse liver, as evidenced by the upregulation of GSDMD-N protein levels; moreover, this pyroptotic effect induced by 100 nm PS-NPs was more pronounced compared to that of 500 nm PS-NPs. Mechanistically, exposure to 100 nm and 500 nm PS-NPs resulted in an upregulation of TXNIP protein expression, thereby activating NLRP3 inflammasome and subsequently inducing inflammatory responses and pyroptosis. Notably, following the termination of PS-NPs exposure and a subsequent recovery period of 50 days, PS-NPs-mediated inflammation and pyroptosis via TXNIP/NLRP3 pathway were effectively ameliorated, even returning to levels close to the baseline. Collectively, our findings provide novel evidence for the size-dependence and reversibility of NPs-induced hepatic pyroptosis through TXNIP/NLRP3/GSDMD pathway in vivo.

[Occurrence and Risk Assessment of N-nitrosamines and Their Precursors in Qingjiang River Basin].

N-nitrosamines are a type of nitrogen-containing organic pollutant with high carcinogenicity and mutagenicity. In the main drinking water sources of small and medium-sized towns in China, the contamination levels of N-nitrosamines remain unclear. In addition, there is still lack of research on the concentration of N-nitrosamines and their precursors in tributary rivers. In this study, eight N-nitrosamines and their formation potentials （FPs） were investigated in the Qingjiang River, which is a primary tributary of the Yangtze River. The sewage discharge sites were also monitored, and the environmental influencing factors, carcinogenic and ecological risks caused by N-nitrosamines, and their precursors were evaluated. The results showed that six N-nitrosamines were detected in water samples of the Qingjiang River, among which NDMA [（10 ±15） ng·L-1], NDEA [（9.3 ±9.3） ng·L-1], and NDBA [（14 ±7.8） ng·L-1] were the dominant N-nitrosamines, whereas seven N-nitrosamines were detected in chloraminated water samples, among which NDMA-FP [（46 ±21） ng·L-1], NDEA-FP [（26 ±8.3） ng·L-1], and NDBA-FP [（22 ±13） ng·L-1] were the dominant N-nitrosamine FPs. The concentrations of N-nitrosamines in the middle reaches of the Qingjiang River were higher than those in the upper and lower reaches. Furthermore, the concentrations of N-nitrosamines in the sample sites of sewage discharge and tributaries were significantly higher than those in other sampling sites. The monitoring results at the direct sewage discharge points indicated that the main source of N-nitrosamines in river water was the sewage carrying N-nitrosamines and their precursors. In addition, the concentrations of the three dominant N-nitrosamines including NDMA, NDBA, and NDEA were positively correlated with each other, mainly because of their similar sewage sources. The average carcinogenic risk to residents due to N-nitrosamine in drinking water sources was 2.4×10-5, indicating a potential carcinogenic risk. Moreover, due to the high concentrations of N-nitrosamine formation potentials in the Qingjiang River, the carcinogenic risk of drinking water may be even higher. The ecological risk assessment showed that the ecological risk quotient values of N-nitrosamines in the Qingjiang River watershed were lower than 0.002, which was negligible.

Charge Generation Dynamics in Organic Photovoltaic Blends under One-Sun-Equivalent Illumination Detected by Highly Sensitive Terahertz Spectroscopy.

Organic photovoltaic (OPV) devices attain high performance with nonfullerene acceptors by utilizing the synergistic dual channels of charge generation that originate from excitations in both the donor and acceptor materials. However, the specific intermediate states that facilitate both channels are subject to debate. To address this issue, we employ time-resolved terahertz spectroscopy with improved sensitivity (ΔE/E < 10-6), enabling direct probing of charge generation dynamics in a prototypical PM6:Y6 bulk heterojunction system under one-sun-equivalent excitation density. Charge generation arising from donor excitations is characterized with a rise time of ∼9 ps, while that from acceptor excitations shows a rise time of ∼18 ps. Temperature-dependent measurements further reveal notably distinct activation energies for these two charge generation pathways. Additionally, the two channels of charge generation can be substantially manipulated by altering the ratio of bulk to interfaces. These findings strongly suggest the presence of two distinct intermediate states: interfacial and intramoiety excitations. These states are crucial in mediating the transfer of electrons and holes, driving charge generation within OPV devices.

Association between ambient temperature and cause-specific mortality: An individual-level case-crossover study in Suzhou, China.

The changing climate poses a growing challenge to the population health. The objective of this study was to assess the association between ambient temperature and cause-specific mortality in Suzhou. Based on the non-accidental mortality data collected during 2008-2022 in Suzhou, China, this study utilized an individual-level case-crossover design to evaluate the associations of temperature with cause-specific mortality. We applied a distributed lag nonlinear model with a maximum lag of 14 days to account for lag effects. Mortality risk due to extreme cold (<2.5th percentile) and extreme heat (>97.5th percentile) was analyzed. A total of 634,530 non-accidental deaths were analyzed in this study. An inverse J-shaped exposure-response relationship was observed between ambient temperature and non-accidental mortality, with the minimum mortality temperature (MMT) at 29.1℃. The relative risk (RR) of mortality associated with extreme cold (2.5th percentile) was 1.37 [95 % confidence interval (CI): 1.30, 1.44], higher than estimate of 1.09 (95 %CI: 1.07, 1.11) for extreme heat (97.5th percentile) relative to the MMT. Heat effect lasted for 2-3 days, while cold effect could persist for almost 14 days. Higher mortality risk estimates were observed for cardiorespiratory deaths compared to total deaths, with statistically significant between-group differences. Consequently, this study provides first-hand evidence on the associations between ambient temperatures and mortality risks from various causes, which could help local government and policy-makers in designing targeted strategies and public health measures against the menace of climate change.

Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

BACKGROUND AIMS: Imbalance in lipid metabolism is the main cause of nonalcoholic fatty liver disease (NAFLD). While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of interleukin-22 (IL-22) protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH RESULTS: This study shows hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout (HKO) mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly, 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition via the activating transcription factor 3 (ATF3)/oxysterol 7 alpha-hydroxylase (CYP7B1) axis. Notably, 3ß HCA facilitates lipogenesis in MPHs and human liver organoids (HLOs) by activating LXR-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring CYP7B1 or silencing hepatic ATF3 reduces both hepatic 3ß HCA and lipid contents in HKO mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an ATF3/CYP7B1-dependent manner, and establish a link between 3ß HCA and hepatic lipid homeostasis.

Ancestral origins and admixture history of Kazakhs.

Kazakh people, like many other populations that settled in Central Asia, demonstrate an array of mixed anthropological features of East Eurasian (EEA) and West Eurasian (WEA) populations, indicating a possible scenario of biological admixture between already differentiated EEA and WEA populations. However, their complex biological origin and genomic makeup, as well as their genetic interaction with surrounding populations, are not well understood. In an attempt to decipher their genetic structure and population history, we conducted, to our knowledge, the first whole-genome sequencing study of Kazakhs residing in Xinjiang (KZK). We demonstrated that KZK derived their ancestries from four ancestral source populations: East Asian (∼39.7%), West Asian (∼28.6%), Siberian (∼23.6%), and South Asian (∼8.1%). The recognizable interactions of EEA and WEA ancestries in Kazakhs were dated back to the 15th century BCE. Kazakhs were genetically distinctive from Uyghurs in terms of their overall genomic makeup, although the two populations were closely related in genetics, and both showed a substantial admixture of EEA and WEA ancestries. Notably, we identified a considerable sex-biased admixture, with an excess of western males and eastern females contributing to the KZK gene pool. We further identified a set of genes that showed remarkable differentiation in KZK from the surrounding populations, including those associated with skin color (SLC24A5, OCA2), essential hypertension (HLA-DQB1), hypertension (MTHFR, SLC35F3), and neuron development (CNTNAP2). These results advance our understanding of the complex history of contacts between Western and Eastern Eurasians, especially those situated along the old Silk Road.

A cross-sectional study of predictive factors of health literacy among rheumatoid arthritis patients in China.

Objective: To investigate the factors that influence health literacy (HL) among Chinese patients with rheumatoid arthritis (RA) and furnish theoretical underpinnings for the development of intervention strategies aimed at enhancing patients' quality of life. Methods: From May 2022 to December 2022, a comprehensive survey was conducted among both outpatients and inpatients diagnosed with (RA) in a tertiary hospital in China. The survey utilized various instruments, including a general information questionnaire, a chronic disease patient health literacy scale, the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Chinese-translated Rheumatoid Arthritis Self-Efficacy Scale, the Chinese-translated Rheumatoid Arthritis Stigma Scale, and the Chinese-translated Compliance Questionnaire for Rheumatology Treatments. Results: The average scores of HL, self-efficacy, medication adherence, and disability index were 83.54 ± 17.43, 84.91 ± 14.37, 70.16 ± 11.24, and 0.26 ± 0.44, respectively. HL in Chinese RA patients was negatively correlated with age, erythrocyte sedimentation rate (ESR), number of tender joints, number of swollen joints, and disease activity, while positively correlated with self-efficacy and medication adherence. Age, disease activity, disability index, self-efficacy, and medication adherence are predictive factors of HL, and a predictive model has been initially constructed. Conclusion: In the management of RA, healthcare professionals should develop and implement effective intervention measures by focusing on improving medication adherence, enhancing patients' self-efficacy, improving patients' physical function, and reducing disease activity. This will help enhance the health literacy and promote clinical outcomes in RA patients.

Adeno-associated-virus-mediated delivery of CRISPR-CasRx induces efficient RNA knockdown in the mouse testis.

Rationale: In male mammals, many developmental-stage-specific RNA transcripts (both coding and noncoding) are preferentially or exclusively expressed in the testis, where they play important roles in spermatogenesis and male fertility. However, a reliable platform for efficiently depleting various types of RNA transcripts to study their biological functions during spermatogenesis in vivo has not been developed. Methods: We used an adeno-associated virus serotype nine (AAV9)-mediated CRISPR-CasRx system to knock down the expression of exogenous and endogenous RNA transcripts in the testis. Virus particles were injected into the seminiferous tubules via the efferent duct. Using an autophagy inhibitor, 3-methyladenine (3-MA), we optimized the AAV9 transduction efficiency in germ cells in vivo. Results: AAV9-mediated delivery of CRISPR-CasRx effectively and specifically induces RNA transcripts (both coding and noncoding) knockdown in the testis in vivo. In addition, we showed that the co-microinjection of AAV9 and 3-MA into the seminiferous tubules enabled long-term transgene expression in the testis. Finally, we found that a promoter of Sycp1 gene induced CRISPR-CasRx-mediated RNA transcript knockdown in a germ-cell-type-specific manner. Conclusion: Our results demonstrate the efficacy and versatility of the AAV9-mediated CRISPR-CasRx system as a flexible knockdown platform for studying gene function during spermatogenesis in vivo. This approach may advance the development of RNA-targeting therapies for conditions affecting reproductive health.

Chirally Selective and Switchable Luminescence from Achiral Quantum Emitters on Suspended Twisted Stacking Metasurfaces.

Dynamic control of circularly polarized photoluminescence has aroused great interest in quantum optics and nanophotonics. Chiral plasmonic metasurfaces enable the manipulation of the polarization state via plasmon-photon coupling. However, current plasmonic light-emitting metasurfaces for effective deterministic modulation of spin-dependent emission at near-infrared wavelengths are underexplored in terms of dissymmetry and tunability. Here, we demonstrate a microfluidic hybrid emitting system of a suspended twisted stacking metasurface coated with PbS quantum dots. The suspended metasurface is fabricated with a single step of electron beam exposure, exhibiting a strong optical chirality of 309° µm-1 with a thickness of less than λ/10 at key spectral locations. With significant chiral-selective interactions, enhanced photoluminescence is achieved with strong dissymmetry in circular polarization. The dissymmetry factor of the induced circularly polarized emission can reach 1.54. More importantly, altering the refractive index of the surrounding medium at the bottom surface of the metasurface can effectively manipulate the chiroptical responses of the hybrid system, hence leading to chirality-reversed emission. This active hybrid emitting system could be a resultful platform for chirality-switchable light emission from achiral quantum emitters, holding great potential for anticounterfeiting, biosensing, light sources, imaging, and displays.

Examining the relationship between alterations in plasma cholesterol, vascular endothelin-1 levels, and the severity of sepsis in children: An observational study.

Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.

Adaptive evolution of two distinct adaptive haplotypes of Neanderthal origin at the immunoglobulin heavy-chain locus in East Asian and European populations.

Immunoglobulins have a crucial role in humoral immunity. Two recent studies have reported a high-frequency Neanderthal-introgressed haplotype throughout Eurasia and a high-frequency Neanderthal-introgressed haplotype specific to southern East Asia at the immunoglobulin heavy-chain (IGH) gene locus on chromosome 14q32.33. Surprisingly, we found the previously reported high-frequency Neanderthal-introgressed haplotype does not exist throughout Eurasia. Instead, our study identified two distinct high-frequency haplotypes of putative Neanderthal origin in East Asia and Europe, although they shared introgressed alleles. Notably, the alleles of putative Neanderthal origin reduced the expression of IGHG1 and increased the expression of IGHG2 and IGHG3 in various tissues. These putatively introgressed alleles also affected the production of IgG1 upon antigen stimulation and increased the risk of systemic lupus erythematosus. Additionally, the greatest genetic differentiation across the whole genome between southern and northern East Asians was observed for the East Asian haplotype of putative Neanderthal origin. The frequency decreased from southern to northern East Asia and correlated positively with the genome-wide proportion of southern East Asian ancestry, indicating that this putative positive selection likely occurred in the common ancestor of southern East Asian populations before the admixture with northern East Asian populations.

Sarcopenia adversely impacts clinical outcomes in patients undergoing pancreaticoduodenectomy: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is a syndrome marked by a gradual and widespread reduction in skeletal muscle mass and strength, as well as a decline in functional ability, which is associated with malnutrition, hormonal changes, chronic inflammation, disturbance of intestinal flora, and exercise quality. Pancreatoduodenectomy is a commonly employed clinical intervention for conditions such as pancreatic head cancer, ampulla of Vater cancer, and cholangiocarcinoma, among others, with a notably high rate of postoperative complications. Sarcopenia is frequent in patients undergoing pancreatoduodenectomy. However, data regarding the effects of sarcopenia in patients undergoing pancreaticoduodenectomy (PD) are both limited and inconsistent. AIM: To assess the influence of sarcopenia on outcomes in patients undergoing PD. METHODS: The PubMed, Cochrane Library, Web of Science, and Embase databases were screened for studies published from the time of database inception to June 2023 that described the effects of sarcopenia on the outcomes and complications of PD. Two researchers independently assessed the quality of the data extracted from the studies that met the inclusion criteria. Meta-analysis using RevMan 5.3.5 and Stata 14.0 software was conducted. Forest and funnel plots were used, respectively, to demonstrate the outcomes of the sarcopenia group vs the non-sarcopenia group after PD and to evaluate potential publication bias. RESULTS: Sixteen studies encompassing 2381 patients were included in the meta-analysis. The patients in the sarcopenia group (n = 833) had higher overall postoperative complication rates [odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.95-5.99, P < 0.0001], higher Clavien-Dindo class ≥ III major complication rates (OR = 1.41, 95%CI: 1.04-1.90, P = 0.03), higher bacteremia rates (OR = 4.46, 95%CI: 1.42-13.98, P = 0.01), higher pneumonia rates (OR = 2.10, 95%CI: 1.34-3.27, P = 0.001), higher pancreatic fistula rates (OR = 1.42, 95%CI: 1.12-1.79, P = 0.003), longer hospital stays (OR = 2.86, 95%CI: 0.44-5.28, P = 0.02), higher mortality rates (OR = 3.17, 95%CI: 1.55-6.50, P = 0.002), and worse overall survival (hazard ratio = 2.81, 95%CI: 1.45-5.45, P = 0.002) than those in the non-sarcopenia group (n = 1548). However, no significant inter-group differences were observed regarding wound infections, urinary tract infections, biliary fistulas, or postoperative digestive bleeding. CONCLUSION: Sarcopenia is a common comorbidity in patients undergoing PD. Patients with preoperative sarcopenia have increased rates of complications and mortality, in addition to a poorer overall survival rate and longer hospital stays after PD.

Controlling glycolysis to generate characteristic volatile organic compounds of lung cancer cells.

Characteristic volatile organic compounds (VOCs) are anticipated to be used for the identification of lung cancer cells. However, to date, consistent biomarkers of VOCs in lung cancer cells have not been obtained through direct comparison between cancer and healthy groups. In this study, we regulated the glycolysis, a common metabolic process in cancer cells, and employed solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS) combined with untargeted analysis to identify the characteristic VOCs shared by cancer cells. The VOCs released by three types of lung cancer cells (A549, PC-9, NCI-H460) and one normal lung epithelial cell (BEAS-2B) were detected using SPME-GC-MS, both in their resting state and after treatment with glycolysis inhibitors (2-Deoxy-D-glucose, 2-DG/3-Bromopyruvic acid, 3-BrPA). Untargeted analysis methods were employed to compare the VOC profiles between each type of cancer cell and normal cells before and after glycolysis regulation. Our findings revealed that compared to normal cells, the three types of lung cancer cells exhibited three common differential VOCs in their resting state: ethyl propionate, acetoin, and 3-decen-5-one. Furthermore, under glycolysis control, a single common differential VOC-acetoin was identified. Notably, acetoin levels increased by 2.60-3.29-fold in all three lung cancer cell lines upon the application of glycolysis inhibitors while remaining relatively stable in normal cells. To further elucidate the formation mechanism of acetoin, we investigated its production by blocking glutaminolysis. This interdisciplinary approach combining metabolic biochemistry with MS analysis through interventional synthetic VOCs holds great potential for revolutionizing the identification of lung cancer cells and paving the way for novel cytological examination techniques.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

Advance on Chinese Medicine for Hypertensive Renal Damage: Focus on the Complex Molecular Mechanisms.

Hypertensive renal damage (HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine (CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.