A wide-range UAC sensor for the classification of hyperuricemia in spot samples.

Hyperuricemia (HUA) has received wide attention as an independent risk factor for various chronic diseases. HUA is usually asymptomatic, and the related damage can be reduced by effective classification and treatment according to uric acid clearance (UAC). UAC is a calculated ratio based on the uric acid level in blood and urine. This important method is not universally used due to the inconvenience of collecting 24-h urine samples in the clinic, and most sensors are limited by the need for wide ranges and for two testing samples. In this study, a pH-sensitive urate oxidase-modified electrochemical sensor with filter membrane was proposed to calculate UAC by detecting uric acid in blood and urine. The results demonstrated that the sensor had high selectivity for uric acid with a detection limit of 0.25 µM in 5 µL spot sample, the wide linear range was 2.5-7000 µM, and the impact of the sample pH was calibrated. The linear correlation of the measurement results between the UAC sensor and clinical instrument was higher than 0.980 for 87 patients. The change in UAC in spot urine may reflect alteration in body-transport mechanisms. Thus, the UAC sensor may open a new window for the management of HUA and broaden its application in point-of-care testing.

A new multi-parameter imaging platform for in vivo drug efficacy evaluation of ischemic stroke.

Ischemic stroke with high incidence and disability rate severely endangers human health. Current clinical treatment strategies are quite limited, new drugs for ischemic stroke are urgently needed. However, most existing methods for the efficacy evaluation of new drugs possess deficiencies of divorcing from the true biological context, single detection indicator and complex operations, leading to evaluation biases and delaying drug development process. In this work, leveraging the advantages of fluorescence imaging with non-invasive, real-time, in-situ, high selectivity and high sensitivity, a new multi-parameter simultaneous fluorescence imaging platform (MPSFL-Platform) based on two fluorescence materials was constructed to evaluate the efficacy of new drug for ischemic stroke. Through simultaneous fluorescence observing three key indicators of ischemic stroke, malondialdehyde (MDA), formaldehyde (FA), and monoamine oxidase A (MAO-A), the efficacy evaluations of three drugs for ischemic stroke were real-time and in-situ performed. Compared with edaravone and butylphthalide, edaravone dexborneol exhibited better therapeutic effect by using MPSFL-Platform. The successful establishment of MPSFL-Platform is serviceable to accelerate the conduction of preclinical trial and the exploration of pathophysiology mechanism for drugs related to ischemic stroke and other brain diseases, which is perspective to promote the efficiency of new drug development.

Opportunities and challenges for ribosome-inactivating proteins in traditional Chinese medicine plants.

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.

Genomes of cultivated and wild Capsicum species provide insights into pepper domestication and population differentiation.

Pepper (Capsicum spp.) is one of the earliest cultivated crops and includes five domesticated species, C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. Here, we report a pepper graph pan-genome and a genome variation map of 500 accessions from the five domesticated Capsicum species and close wild relatives. We identify highly differentiated genomic regions among the domesticated peppers that underlie their natural variations in flowering time, characteristic flavors, and unique resistances to biotic and abiotic stresses. Domestication sweeps detected in C. annuum var. annuum and C. baccatum var. pendulum are mostly different, and the common domestication traits, including fruit size, shape and pungency, are achieved mainly through the selection of distinct genomic regions between these two cultivated species. Introgressions from C. baccatum into C. chinense and C. frutescens are detected, including those providing genetic sources for various biotic and abiotic stress tolerances.

Blooming characteristics and breeding system of an invasive plant Gaura parviflora.

The invasiveness and dissemination of exotic species are strongly influenced by its sexual reproduction characteristics, including blooming characteristics and breeding system. Exploring the association of these sexual reproductive traits with invasiveness would be helpful for revealing the mechanism of its successful invasion. We examined the blooming characteristics and breeding system of Gaura parviflora based on field observations, out-crossing index (OCI) estimation, and hand-pollination experiments. The results showed flowering duration of the G. parviflora population (flowering period) was short (more than 3 months). The life span of single flower (floral longevity) was 40.46 h. Its flower diameter was 3.99 mm. Over seven flowers in bloom per inflorescence and most individuals often bloomed synchronously, which showed a 'mass-flowering pattern'. The changing trend of pollen and stigma vitality was relatively similar, but the duration of stigma vitality was 2 h longer than that of pollen. The stigma and the anthers were close to each other at the initial flowering stage, but the stigma removed from the anthers at the full-blooming stage with the style curving downwards. Many pollinators visited flowers in late full-blooming stage, which were mainly Apis mellifera and Syrphidae spp. Their average visiting frequency was 9.8 times·m-2·h-1. The fruit set in natural pollination after emasculation treatment (insect or wind pollination) was signi-ficantly higher than that in bagged and emasculation treatment, and the treatment of emasculated and bagged with nylon net (excluding insect pollination) could also bear fruits, indicating possible existence of ambophily in G. parviflora. The results of pollen ovule ratio (P/O) mensuration, OCI estimation and hand-pollination experiments showed that its mating system type belonged to additive mixed mating system. So, its characteristics, such as smaller flower size, shorter floral longevity and flowering period, were conducive to allocating more resources to plant growth and seed development, which would help improve its total fitness. The changes of spatial position of male and female organs not only avoided interference between male and female functions, but also created opportunities for stigmas to receive outcross pollen. In addition, the 'mass-flowering pattern' was conducive to attracting pollinators. The pollination mechanism of ambophily was helpful to ensure cross-pollination. The additive mixed mating system could provide double reproductive assurance for this species. These reproductive characteristics were significant for the successful invasion and expansion of G. parviflora.

Polyphosphate promotes oxidation resistance of ppk-expressing transgenic rice in low phosphorus culture.

Phosphorus (P) plays a crucial role in plant growth. Insufficient availability of inorganic phosphate (Pi) can significantly impact crop yields. To address this, we previously developed transgenic rice expressing the low polyphosphate kinase gene (ppk) - known as ETRS - to enhance the efficiency of P resource utilization. Previous studies have shown that ETRS thrives and presents high yields in the low P culture. ETRS and wild-type rice (WT) were cultivated to the heading stage at 15 µM of P in the low P (LP) culture and 300 µM of P in the normal culture (CK) to identify the molecular pathways behind low P tolerance. Our findings revealed that polyphosphate (polyP) significantly enhanced the growth performance of ETRS in the LP culture. This enhanced tolerance can be attributed to polyP's capacity to mitigate oxidative damage induced by LP. This was evidenced by the reduction in levels of superoxide radicals, hydrogen peroxide, and malondialdehyde. PolyP also improved the antioxidant capacity of ETRS under LP stress by regulating enzymatic antioxidants viz., superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as non-enzymatic antioxidants such as ascorbate (AsA) and glutathione (GSH). In addition, transcriptomics analysis suggested that polyP synthesis positively promoted the expressions of SOD, POD, and CAT related genes and played an active role in regulating the expression of AsA-GSH cycle system related genes in ETRS in the LP culture. These results strongly support the notion that polyP within ETRS mitigates oxidative damage through enhancement of the antioxidant system, ultimately bolstering tolerance to LP conditions.

Approaches of laparoscopic anatomical liver resection of segment 8 for hepatocellular carcinoma: A retrospective cohort study of short-term results at multiple centers in China.

BACKGROUND: Laparoscopic anatomical liver resection of segment 8 (LALR-S8) remains a challenge for anatomical laparoscopic segmentectomy. Most current reports on LALR-S8 are case series using one surgical approach, and there is a lack of multicenter data on identifying intersegmental planes using different approaches. In this study, we aimed to elucidate the short-term results of three different approaches for LALR-S8 for hepatocellular carcinoma (HCC), focusing on intersegmental plane determination, and to reflect on current practice regarding different approaches at multiple centers in China. MATERIALS AND METHODS: The clinical cohort data of 122 patients who underwent LALR-S8 for HCC at seven leading centers in China were retrospectively analyzed. The surgical procedures of all approaches were summarized and standardized according to the method of the Glissonean pedicle of segment 8 identification. The postoperative short-term outcomes and oncological results of the three approaches were evaluated and compared. RESULTS: Three approaches were used: laparoscopic ultrasonography-guided indocyanine green (ICG) fluorescent positive staining approach (11/122, 9.02%), hepatic vein-guided approach (99/122, 81.15%), and Glissonean ICG fluorescent negative staining approach (12/122, 9.83%). Seven (5.73%) patients experienced complications according to the Clavien-Dindo (CD) classification, and the rate of grade ≥IIIa complications was 2.46%. The R0 resection rates among the groups (margin >1 mm) and the margin width showed no statistical difference. CONCLUSION: LALR-S8 is safe and feasible for treating HCC under standardized surgical techniques and appropriate surgical approaches. The three reported approaches had comparable short-term oncological outcomes, while the hepatic vein-guided approach was most commonly used.

Improving the developmental competences of porcine parthenogenetic embryos by Notoginsenoside R1-induced enhancement of mitochondrial activity and alleviation of proapoptotic events.

Notoginsenoside R1 (NGR1), derived from the Panax notoginseng root and rhizome, exhibits diverse pharmacological influences on the brain, neurons, and osteoblasts, such as antioxidant effects, mitochondrial function protection, energy metabolism regulation, and inhibition of oxygen radicals, apoptosis, and cellular autophagy. However, its effect on early porcine embryonic development remains unclear. Therefore, we investigated NGR1's effects on blastocyst quality, reactive oxygen species (ROS) levels, glutathione (GSH) levels, mitochondrial function, and embryonic development-related gene expression in porcine embryos by introducing NGR1 during the in vitro culture (IVC) of early porcine embryos. Our results indicate that an addition of 1 µM NGR1 significantly increased glutathione (GSH) levels, blastocyst formation rate, and total cell number and proliferation capacity; decreased ROS levels and apoptosis rates in orphan-activated porcine embryos; and improved intracellular mitochondrial distribution, enhanced membrane potential, and reduced autophagy. In addition, pluripotency-related factor levels were elevated (NANOG and octamer-binding transcription factor 4 [OCT4]), antioxidant-related genes were upregulated (nuclear factor-erythroid 2-related factor 2 [NRF2]), and apoptosis- (caspase 3 [CAS3]) and autophagy-related genes (light chain 3 [LC3B]) were downregulated. These results indicate that NGR1 can enhance early porcine embryonic development by protecting mitochondrial function.

Effects of exogenous spermidine on autophagy and antioxidant capacity in ovaries and granulosa cells of Sichuan white geese.

Autophagy can inhibit ovarian senescence induced by oxidative stress and regulate follicle development and atresia, but its mechanism is still unclear. Exogenous spermidine can induce autophagy and scavenge reactive oxygen species (ROS). In this experiment, oxidative stress in Sichuan white geese ovaries and follicular granulosa cells (GCs) were caused by 3-nitropropionic acid (3-NPA) and spermidine was added to explore the effect of exogenous spermidine inducing autophagy and inhibiting oxidative stress in vivo and in vitro. Research results showed that putrescine, spermidine and spermine contents in goose ovaries in the group treated with spermidine combined with 3-NPA were 2.70, 1.94 and 1.70 times higher than those in the group treated with 3-NPA, respectively (P < 0.05). The contents of spermidine and spermine in GCs were 1.37 and 0.89 times higher in the spermidine in combination with the 3-NPA group than in the 3-NPA group, respectively (P < 0.05). LC3 and p62 were mainly expressed in the follicular granulosa layer. The LC3-II/I ratio and p62 level in GCs in the spermidine combined with 3-NPA treatment group were 1.37 and 0.77 times higher than that of the 3-NPA treatment group, respectively (P < 0.05). 3-NPA treatment significantly increased ROS level and the apoptosis rate in GCs, while the combined treatment of spermidine and 3-NPA reversed this change (P < 0.05). In conclusion, spermidine alleviated the oxidative damage induced by 3-NPA by improving the antioxidant capacity of ovaries and follicular GCs of Sichuan white geese and may be alleviated by inducing autophagy in GCs.

Association of retinopathy with risk of all-cause and specific-cause mortality in the National Health and Nutrition Examination Survey, 2005 to 2008.

Objective: This study aimed to elucidate the relationship between retinopathy status or severity and the all-cause and specific-cause mortality risk based on the updated National Health and Nutrition Examination Survey (NHANES) database and 2019 Public Access Link mortality file. Methods: In this prospective cohort study, a total of 6,797 participants aged over 40 years based on NHANES 2005-2008 were analyzed. The severity of retinopathy was classified into 4 grades-no retinopathy, mild non-proliferative retinopathy (NPR), moderate to severe NPR, and proliferative retinopathy (PR). Multiple covariate-adjusted Cox proportional hazards regression models and Fine and Gray competing risk regression models were used to assess the all-cause and cause-specific mortality risks, respectively. The propensity score matching (PSM) approach was also applied additionally to adequately balance between-group covariates to validate our findings. Results: A final total of 4,808 participants representing 18,282,772 United States (US) non-hospitalized participants were included for analysis, 50.27% were male (n = 2,417), 55.32% were non-hispanic white (n = 2,660), and mean [SE] age, 56.10 [0.40] years. After a median follow-up of 12.24 years (interquartile range, 11.16-13.49 years), 1,164 participants died of all-cause mortality, of which 941 (80.84%) died without retinopathy and 223 (19.16%) died with retinopathy at baseline. The presence of retinopathy was associated with increased all-cause mortality, cardiovascular disease (CVD), and diabetes mellitus (DM)-specific mortality, and the results remain consistent after PSM. Severity analysis showed that only mild NPR was associated with an increased all-cause mortality risk (hazard ratio (HR) = 2.01; 95% confidence interval (CI), 1.00-4.03), while increased CVD and DM-specific mortality risk were associated with all grades of retinopathy and were exponentially greater with increasing retinopathy severity, and the trend test was also significant (P for trend 0.004 and 0.04, respectively). Discussion: Our findings suggest that the diagnosis of retinopathy is an independent risk factor for all-cause mortality in people over 40 years old. Retinopathy grading is significantly associated with the survival risk of patients with CVD or DM, it can be a valuable predictor in the stratified management and risk warning of CVD or DM patients, as well as in the monitoring of systemic vasculopathy status.

The Study on the Morphology and Compression Properties of Microcellular TPU/Nanoclay Tissue Scaffolds for Potential Tissue Engineering Applications.

Thermoplastic polyurethane (TPU) materials have shown promise in tissue engineering applications due to their mechanical properties and biocompatibility. However, the addition of nanoclays to TPU can further enhance its properties. In this study, the effects of nanoclays on the microstructure, mechanical behavior, cytocompatibility, and proliferation of TPU/nanoclay (TPUNC) composite scaffolds were comprehensively investigated. The dispersion morphology of nanoclays within the TPU matrix was examined using transmission electron microscopy (TEM). It was found that the nanoclays exhibited a well-dispersed and intercalated structure, which contributed to the improved mechanical properties of the TPUNC scaffolds. Mechanical testing revealed that the addition of nanoclays significantly enhanced the compressive strength and elastic resilience of the TPUNC scaffolds. Cell viability and proliferation assays were conducted using MG63 cells cultured on the TPUNC scaffolds. The incorporation of nanoclays did not adversely affect cell viability, as evidenced by the comparable cell numbers between nanoclay-filled and unfilled TPU scaffolds. The presence of nanoclays within the TPUNC scaffolds did not disrupt cell adhesion or proliferation. The incorporation of nanoclays improved the dispersion morphology, enhanced mechanical performance, and maintained excellent biocompatibility. These findings suggest that TPUNC composites have great potential for tissue engineering applications, providing a versatile and promising scaffold material for regenerative medicine.

Corrigendum: Superiority of integrated cervicothoracic immobilization in the setup of lung cancer patients treated with supraclavicular station irradiation.

[This corrects the article DOI: 10.3389/fonc.2023.1135879.].

Effect of SGLT2 inhibitors on fractures, BMD, and bone metabolism markers in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

This meta-analysis aims to evaluate the impact of Sodium Glucose Transporter 2 (SGLT2) inhibitors on fractures, bone mineral density (BMD), and bone metabolism markers in type 2 diabetes mellitus (T2DM) patients. Pooled relative risk (RR) with 95% confidence interval (CI) assessed the relationship between SGLT2 inhibitors and fracture risk. Weighted mean difference (WMD) with 95% CI explored the correlation between SGLT2 inhibitors and BMD, as well as bone metabolism markers. A total of 20 randomised controlled trials (RCTs) involving 12,764 patients were analysed. No significant association emerged between SGLT2 inhibitor use and elevated fracture risk (pooled RR = 1.21, 95% CI [0.95, 1.54], I2 = 22%). Furthermore, SGLT2 inhibitors exhibited no substantial effects on BMD changes at the lumbar spine (WMD = -0.02, 95% CI [-0.38, 0.34]), femoral neck (WMD = 0.11, 95% CI [-0.28, 0.50]), total hip (WMD = -0.20, 95% CI [-0.41, 0.01]), and distal forearm (WMD = -0.20, 95% CI [-0.62, 0.22]). Similarly, no notable impact of SGLT2 inhibitors on bone metabolism markers, including CTX (WMD = 0.04, 95% CI [-0.02, 0.09]), P1NP (WMD = 1.06, 95% CI [-0.44, 2.57]), PTH (WMD = 0.34, 95% CI [-0.07, 0.75]), calcium (WMD = 0.01, 95% CI [-0.02, 0.04]), and phosphate (WMD = 2.37, 95% CI [-0.76, 5.49]). The findings suggest that the utilization of SGLT2 inhibitors is not significantly linked to an elevated risk of fractures in individuals with T2DM. However, further clinical investigations and extended follow-up periods are warranted to establish more conclusive determinations.

Reconstructing 3d-Metal Electrocatalysts through Anionic Evolution in Zinc-Air Batteries.

As one of the promising sustainable energy storage systems, academic research on rechargeable Zn-air batteries has recently been rejuvenated following development of various 3d-metal electrocatalysts and identification of their dynamic reconstruction toward (oxy)hydroxide, but performance disparity among catalysts remains unexplained. Here, this uncertainty is addressed through investigating the anionic contribution to regulate dynamic reconstruction and battery behavior of 3d-metal selenides. Comparing with the alloy counterpart, anionic chemistry is identified as a performance promoter and further exploited to empower Zn-air batteries. Based on theoretical modeling, Se-resolved operando spectroscopy, and advanced electron microscopy, a three-step Se evolution is established, consisting of oxidation, leaching, and recoordination. The process generates an amorphous (oxy)hydroxide with O-sharing bonded Se motifs that triggers charge redistribution at metal sites and lowers the energetic barrier of their current-driven redox. A pervasive concept of Se back-feeding is then proposed to describe the underlying chemistry for 3d-metal selenides with diversity in crystals or compositions, and the feasibility to fine-tune their behavior is also presented.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study.

BACKGROUND: We aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy. METHODS: This study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect. RESULTS: A total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54-72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282-3.660, P = 0.004; HR 1.583, 95% CI 0.985-2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725). CONCLUSIONS: Perineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Case report: A case of brucellosis misdiagnosed as coronavirus disease 2019/influenza in China.

Brucellosis is an important zoonosis and a multisystem disease. The signs and symptoms of brucellosis are not specific. In the clinical, brucellosis is often ignored and misdiagnosed. We report a case of brucellosis who was misdiagnosed as coronavirus disease 2019 (COVID-19)/influenza and received delayed treatment during strict COVID-19 control. The neglect of other diseases due to COVID-19 and empirical diagnosis and treatment by medical staff are part of the reasons for misdiagnosis. Otherwise, the normal erythrocyte sedimentation rate (ESR), increased white blood cell count (WBC), and increased neutrophil count (NEUT) of this patient was also a cause of misdiagnosis, which is an important reminder for diagnosis. For patients with the unknown origin of fever and other symptoms related to brucellosis, especially those from endemic areas of brucellosis, brucellosis screening is a priority item, and grassroots doctors should be vigilant and standardize the diagnosis and treatment based on epidemiology history, clinical manifestation, and laboratory tests according to the diagnostic criteria of brucellosis.

Association between ADAMTS14_rs4747096 gene polymorphism and bone mineral density of Chinese Han population residing in fluorine exposed areas in ShanXi Province, China.

This study aimed to investigate the effects of fluorine and ADAMTS14_rs4747096 on bone mineral density (BMD). The survey was explored in a cross-sectional case-control study conducted in Shanxi, China. The BMD was measured by an ultrasonic bone mineral density instrument. The urine fluoride concentration was detected using the fluoride ion electrode. ADAMTS14_rs4747096 polymorphism was examined by multiplex polymerase chain reaction (PCR) and sequencing. The multinomial logistic regressions found that the urine fluoride was a risk factor for osteopenia (OR = 1.379, 95% CI: 1.127-1.687, P = 0.0018), osteoporosis (OR = 1.480, 95% CI: 1.1138-1.926, P = 0.0035), and rs4747096 AG + GG genotype increased the risk of osteoporosis (OR = 2.017, 95% CI: 1.208-3.369, P = 0.0073). In addition, the interaction between urine fluoride and rs4747096 polymorphism on the risk of decreased BMD also was observed. The study suggests that fluoride exposure and mutation G allele in ADAMTS14_rs4747096 may be risk factors for the decrease of BMD. And there is an interaction between the two influencing factors.

Decreasing alcohol use among young adults presenting for service in the U.S. Air Force: An epidemiological surveillance study.

U.S. surveys demonstrate recent decreases in the prevalence of alcohol use and binge drinking among young adults. The current study aims to determine whether similar trends are evident in a similarly aged cohort of service members in the US Air Force to inform ongoing prevention efforts. Participants were 103,240 Air Force personnel in entry-level training between 2016 and 2019. Participants anonymously completed the AUDIT (Alcohol Use Disorder Identification Test) regarding their pre-service drinking. Logistic regression analyses and the Cochran-Armitage test were conducted to measure population trends over the study duration with stratification by age (<21 vs. ≥21) and evaluation of specific alcohol behaviors. Between 2016 and 2019, the proportion of young service members endorsing any alcohol use significantly decreased for both the <21 group (i.e. from 38.9% to 32.6%) and the ≥21 group (i.e. from 80.6% to 77.5%). Among those who endorsed drinking, a decrease over time in binge use was also observed from 46.6% to 37.8% for the <21 group and from 34.2% to 27.5% for the ≥21 group. Responses to other specific alcohol risk items and total AUDIT scores also demonstrated decreases. Binge use and risky drinking remained disproportionately common among those under the legal drinking age. It is encouraging to observe a shift toward abstinence and decreased binge use among this population of young military recruits. However, given the risk for many adverse health and legal consequences in this population, more work is needed to prevent problematic drinking, especially among those under the legal drinking age.

Spatial proximity of Tumor-Immune interactions predicts patient outcome in hepatocellular carcinoma.

BACKGROUND AND AIMS: The fitness and viability of a tumor ecosystem are influenced by the spatial organization of its cells. We aimed to study the structure, architecture, and cell-cell dynamics of the heterogenous liver cancer tumor microenvironment using spatially resolved multiplexed imaging. APPROACH AND RESULTS: We performed co-detection by indexing (CODEX) multiplexed immunofluorescence imaging on 68 hepatocellular carcinoma (HCC) biopsies from Thai patients (TIGER-LC) as a discovery cohort, and then validated the results in an additional 190 HCC biopsies from Chinese patients (LCI). We segmented and annotated 117,270 and 465,632 cells from the TIGER-LC and LCI cohorts, respectively. We observed four groups of TIGER-LC patients (IC1, IC2, IC3, IC4) with distinct tumor-immune cellular interaction patterns. In addition, patients from IC2 and IC4 had much better overall survival than those from IC1 and IC3. Noticeably, tumor and CD8+ T cell interactions were strongly enriched in IC2, the group with the best patient outcomes. Close proximity between tumor and CD8+ T cells was a strong predictor of patient outcome in both the TIGER-LC and the LCI cohorts. Bulk transcriptomic data from 51 of the 68 HCC cases was utilized to determine tumor-specific gene expression features of our classified subtypes. Moreover, we observed that the presence of immune spatial neighborhoods in HCC as a measure of overall immune infiltration is linked to better patient prognosis. CONCLUSIONS: Highly multiplexed imaging analysis of liver cancer reveals tumor-immune cellular heterogeneity within spatial contexts, such as tumor and CD8+ T cell interactions, which may predict patient survival.