Strongly correlated multielectron bunches from interaction with quantum light.

Strongly correlated electron systems are a cornerstone of modern physics, being responsible for groundbreaking phenomena from superconducting magnets to quantum computing. In most cases, correlations in electrons arise exclusively because of Coulomb interactions. In this work, we reveal that free electrons interacting simultaneously with a light field can become highly correlated via mechanisms beyond Coulomb interactions. In the case of two electrons, the resulting Pearson correlation coefficient for the joint probability distribution of the output electron energies is enhanced by more than 13 orders of magnitude compared to that of electrons interacting with the light field in succession (one after another). These highly correlated electrons are the result of momentum and energy exchange between the participating electrons via the external quantum light field. Our findings pave the way to the creation and control of highly correlated free electrons for applications including quantum information and ultrafast imaging.

Effect of humic acid on visible light photocatalytic inactivation of bacteriophage f2 with electrospinning Cu-TiO2 nanofibers: insight into the mechanisms.

Photocatalytic disinfection is a promising technology with low cost and high efficiency. However, most of the current studies on photocatalytic disinfection ignore the widespread presence of natural organic matter (NOM) in water bodies, so the incomplete conclusions obtained may not be applicable. Herein, this paper systematically studied the influence of humic acid (HA), one of the most important components of NOM, on the photocatalytic inactivation of bacteriophage f2 with electrospinning Cu-TiO2 nanofibers. We found that with the addition of HA, the light transmittance of the solution at 550 nm decreased from 94 to 60%, and the band gap of the photocatalyst was increased from 2.96 to 3.05 eV. Compared with reacting without HA, the degradation amount of RNA of f2 decreased by 88.7% after HA was added, and the RNA concentration increased from 1.95 to 4.38 ng·µL-1 after the reaction. Hence, we propose mechanisms of the effect of HA on photocatalytic disinfection: photo-shielding, passivation of photocatalysts, quenching of free radicals, and virus protection. Photo-shielding and photocatalyst passivation lead to the decrease of photocatalyst activity, and the reactive oxygen species (ROSs) (·OH, ·O2-, 1O2, H2O2) are further trapped by HA. The HA in water also can protect the shape of phage f2 and reduce the leakage of protein and the destruction of ribonucleic acid (RNA). This work provides an insight into the mechanisms for the influence of HA in photocatalytic disinfection process and a theoretical basis for its practical application.

Aggressive vertebral hemangiomas contain no adipose tissue resulting in thoracic spine kyphosis: A case report.

RATIONALE: Aggressive vertebral hemangiomas (AVHs) destroy continuous vertebral bodies and intervertebral discs and resulting in spinal kyphosis is extremely rare. The very aggressive behavior was attributable to its significant vascular component and contained no adipose tissue. PATIENT CONCERNS: We report a case of thoracic spine kyphosis of AVHs with multiple vertebral bodies and intervertebral disc destruction in a 45-year-old woman. DIAGNOSES: Based on the imaging studies, the patient underwent surgical removal of this lesion and spinal reconstruction. Histopathology consistent with vertebral hemangioma and contained no adipose. INTERVENTIONS: The patient underwent surgical removal of the lesion and spinal reconstruction. After subperiosteal dissection of the paraspinal muscles and exposure of the laminae, the laminae of the T5-7 vertebrae were removed and exposing the lesion. The lesion was soft and showed cystic changes, completely curetted and autogenous bone was implanted. Vertebroplasty was performed through T3-T9 pedicles bilaterally. Pedicle screw fixation was performed for segmental fixation and fusion. OUTCOMES: After 9 days of operation, the incision healed cleanly and free of pain. She was discharged in good general condition. The patient remained asymptomatic after follow-up 6 months of postoperative. LESSONS: AVHs destroy multiple vertebral bodies and intervertebral discs and resulting in spinal kyphosis is extremely rare.

Carbon fluxes of China's coastal wetlands and impacts of reclamation and restoration.

Coastal wetlands play an important role in regulating atmospheric carbon dioxide (CO2) concentrations and contribute significantly to climate change mitigation. However, climate change, reclamation, and restoration have been causing substantial changes in coastal wetland areas and carbon exchange in China during recent decades. Here we compiled a carbon flux database consisting of 15 coastal wetland sites to assess the magnitude, patterns, and drivers of carbon fluxes and to compare fluxes among contrasting natural, disturbed, and restored wetlands. The natural coastal wetlands have the average net ecosystem exchange of CO2 (NEE) of -577 g C m-2 year-1, with -821 g C m-2 year-1 for mangrove forests and -430 g C m-2 year-1 for salt marshes. There are pronounced latitudinal patterns for carbon dioxide exchange of natural coastal wetlands: NEE increased whereas gross primary production (GPP) and respiration of ecosystem decreased with increasing latitude. Distinct environmental factors drive annual variations of GPP between mangroves and salt marshes; temperature was the dominant controlling factor in salt marshes, while temperature, precipitation, and solar radiation were co-dominant in mangroves. Meanwhile, both anthropogenic reclamation and restoration had substantial effects on coastal wetland carbon fluxes, and the effect of the anthropogenic perturbation in mangroves was more extensive than that in salt marshes. Furthermore, from 1980 to 2020, anthropogenic reclamation of China's coastal wetlands caused a carbon loss of ~3720 Gg C, while the mangrove restoration project during the period of 2021-2025 may switch restored coastal wetlands from a carbon source to carbon sink with a net carbon gain of 73 Gg C. The comparison of carbon fluxes among these coastal wetlands can improve our understanding of how anthropogenic perturbation can affect the potentials of coastal blue carbon in China, which has implications for informing conservation and restoration strategies and efforts of coastal wetlands.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Inadequate pregnancy-specific knowledge among patients with inflammatory bowel disease: A multicenter survey in China.

OBJECTIVES: The perceptions and attitudes of inflammatory bowel disease (IBD) patients towards pregnancy may affect their fertility plan and disease progression. We performed a nationwide multicenter survey of pregnancy-related knowledge among gastroenterologists and IBD patients in China to investigate whether specific educational interventions could improve their understanding and broadly influence fertility plan. METHODS: A cross-sectional questionnaire regarding pregnancy-specific knowledge was carried out among 63 IBD centers in China. Questionnaires were collected from 185 physicians and 609 patients. The patients then received education regarding pregnancy during IBD and filled in the same questionnaire again. Their knowledge regarding pregnancy during IBD was compared before and after education. RESULTS: Compared to physicians, patients' knowledge regarding fertility (39.1% vs 70.8%), imaging examinations (22.8% vs 72.4%), endoscopy performed during pregnancy (19.9% vs 71.4%), and vaccination for infants (16.6% vs 46.5%) was significantly more limited (all P < 0.001). There was a lack of knowledge among gastroenterologists regarding the delivery mode (36.8%), medications (36.8%), and emergency surgery (26.5%) during pregnancy in patients with IBD. After education, the patients showed significant improvement in knowledge regarding medications (26.7% vs 51.7%), fertility (45.0% vs 63.3%), heritability (40.0% vs 58.3%), indications for emergency surgery (15.0% vs 53.3%), imaging examinations during pregnancy (20.0% vs 40.0%), and vaccinations for infants (26.7% vs 45.0%) (all P < 0.05). CONCLUSIONS: Pregnancy-specific IBD knowledge needs to be improved among certain gastroenterologists and patients in China. Educational interventions can partially improve the knowledge levels of the patients.

Activating transcription factor 4: a regulator of stress response in human cancers.

Activating transcription factor 4 (ATF4) is an adaptive response regulator of metabolic and oxidative homeostasis. In response to cellular stress, ATF4 is activated and functions as a regulator to promote cell adaptation for survival. As a transcriptional regulator, ATF4 also widely participates in the regulation of amino acid metabolism, autophagy, redox homeostasis and endoplasmic reticulum stress. Moreover, ATF4 is associated with the initiation and progression of glioblastoma, hepatocellular carcinoma, colorectal cancer, gastric cancer, breast cancer, prostate cancer and lung cancer. This review primarily aims to elucidate the functions of ATF4 and its role in multiple cancer contexts. This review proposes potential therapeutic targets for clinical intervention.

Efficient bubble/precipitate traffic enables stable seawater reduction electrocatalysis at industrial-level current densities.

Seawater electroreduction is attractive for future H2 production and intermittent energy storage, which has been hindered by aggressive Mg2+/Ca2+ precipitation at cathodes and consequent poor stability. Here we present a vital microscopic bubble/precipitate traffic system (MBPTS) by constructing honeycomb-type 3D cathodes for robust anti-precipitation seawater reduction (SR), which massively/uniformly release small-sized H2 bubbles to almost every corner of the cathode to repel Mg2+/Ca2+ precipitates without a break. Noticeably, the optimal cathode with built-in MBPTS not only enables state-of-the-art alkaline SR performance (1000-h stable operation at -1 A cm-2) but also is highly specialized in catalytically splitting natural seawater into H2 with the greatest anti-precipitation ability. Low precipitation amounts after prolonged tests under large current densities reflect genuine efficacy by our MBPTS. Additionally, a flow-type electrolyzer based on our optimal cathode stably functions at industrially-relevant 500 mA cm-2 for 150 h in natural seawater while unwaveringly sustaining near-100% H2 Faradic efficiency. Note that the estimated price (~1.8 US$/kgH2) is even cheaper than the US Department of Energy's goal price (2 US$/kgH2).

New Insights into Aggregation Behaviors of the UV-Irradiated Dissolved Biochars (DBioCs) in Aqueous Environments: Effects of Water Chemistries and Variation in the Hamaker Constant.

The aggregation behavior of ubiquitous dissolved black carbon (DBC) largely affects the fate and transport of its own contaminants and the attached contaminants. However, the photoaging processes and resulting effects on its colloidal stability remain yet unknown. Herein, dissolved biochars (DBioCs) were extracted from common wheat straw biochar as a proxy for an anthropogenic DBC. The influences of UV radiation on their aggregation kinetics were systematically investigated under various water chemistries (pH, electrolytes, and protein). The environmental stability of the DBioCs before and after radiation was further verified in two natural water samples. Hamaker constants of pristine and photoaged DBioCs were derived according to Derjaguin-Landau-Verwey-Overbeek (DLVO) prediction, and its attenuation (3.19 ± 0.15 × 10-21 J to 1.55 ± 0.07 × 10-21 J after 7 days of radiation) was described with decay kinetic models. Pearson correlation analysis revealed that the surface properties and aggregation behaviors of DBioCs were significantly correlated with radiation time (p < 0.05), indicating its profound effects. Based on characterization and experimental results, we proposed a three-stage mechanism (contended by photodecarboxylation, photo-oxidation, and mineral exposure) that DBioCs might experience under UV radiation. These findings would provide an important reference for potential phototransformation processes and relevant behavioral changes that DBC may encounter.

Diurnal emission variation of ozone precursors: Impacts on ozone formation during Sep. 2019.

With the issue of ozone (O3) pollution having increasingly gained visibility and prominence in China, the Chinese government explored various policies to mitigate O3 pollution. In some provinces and cities, diurnal regulations of O3 precursor were implemented, such as shifting O3 precursor emission processes to nighttime and offering preferential refueling at night. However, the effectiveness of these policies remains unverified, and their impact on the O3 generation process requires further elucidation. In this study, we utilized a regional climate and air quality model (WRF-Chem, v4.5) to test three scenarios aimed at exploring the impact of diurnal industry emission variation of O3 precursors on O3 formation. Significant O3 variations were observed mainly in urban areas. Shifting volatile organic compounds (VOCs) to nighttime have slight decreased daytime O3 levels while moving nitrogen oxides (NOx) to nighttime elevates O3 levels. Simultaneously moving both to nighttime showed combined effects. Process analysis indicates that the diurnal variation in O3 was mainly attributed to chemical process and vertical mixing in urban areas, while advection becomes more important in non-urban areas, contributing to the changes in O3 and O3 precursors levels through regional transportation. Further photochemical analysis reveals that the O3 photochemical production in urban areas was affected by reduced daytime O3 precursors emissions. Specifically, decreasing VOCs lowered the daytime O3 production by reducing the ROx radicals (ROx = HO + HO˙2 + RO˙2), whereas decreasing NOx promoted the daytime O3 production by weakening ROx radical loss. Our results demonstrate that diurnal regulation of O3 precursors will disrupt the ROx radical and O3 formation in local areas, resulting in a change in O3 concentration and atmospheric oxidation capacity, which should be considered in formulating new relevant policies.

Effect modification of diet and vitamins on the association between air pollution particles of different diameters and hypertension: A 12-year longitudinal cohort study in densely populated areas of China.

INTRODUCTION: Particulate matter (PM) is identified as one of the exacerbating and triggering factors for hypertension. Diet intake and the consumption of vitamins may potentially moderate the impact of PM on hypertension. METHODS: A 12-year longitudinal cohort study was conducted on a population in densely populated areas of China. Residual balancing with weighted methods was employed to control for time-varying and no time-varying confounding factors. Stratified Cox proportional hazards models were conducted to examine the moderating effects of diet and vitamins on the risk of hypertension with PM. RESULTS: There was a significant positive association between long-term exposure to different diameter PM and the risk of developing hypertension. The hazard ratios (HRs) for hypertension were 1.0200 (95 % CIs: 1.0147, 1.0253) for PM1, 1.0120 (95 % CIs: 1.0085, 1.0155) for PM2.5, and 1.0074 (95 % CIs, 1.0056, 1.0092) for PM10. The diet and vitamins moderated these associations, the intake of healthy foods and vitamins exhibited a significant positive moderating effect on the relationship between PM exposure and hypertension risk. Among all participants, the high intake of fruit (PM1 (HRs: 1.0102, 95 % CIs: 1.0024, 1.0179), PM2.5 (HRs: 1.0060, 95 % CIs: 1.0011, 1.0109), and PM10 (HRs: 1.0044, 95 % CIs: 1.0018, 1.0070)) and vitamin E (PM1 (HRs: 1.0143, 95 % CIs: 1.0063, 1.0223), PM2.5 (HRs:1.0179, 95 % CIs: 1.0003, 1.0166), and PM10 (HRs: 1.0042, 95 % CIs: 1.0008, 1.0075)) with lower risk of hypertension than the overall level and low intake of related foods and vitamins, exhibited a strong positive moderating effect on the relationship between PM and hypertension. Similar trends were observed for the intake of fish, root food, whole grains, eggs, fungus food, vitamin B2, B3. However, Na, meat, sugary and alcoholic exhibited opposite trends. The moderating effect of vitamin E intake was stronger than vitamin B and C. CONCLUSIONS: Diet and vitamins intake may moderate the association between PM exposure and the risk of hypertension in adults.

Abnormal hemoglobin anti-Lepore Hong Kong compound with ß0-thalassemia ameliorate thalassemia severity when co-inherited with α-thalassemia.

Abnormal hemoglobin anti-Lepore Hong Kong is a rare ßδ fusion variants resulting from non-homologous crossover during meiosis. Anti-Lepore Hong Kong is known to consistently exhibit significantly increased level of HbA2. In this study, we used multiplex ligation-dependent probe amplification (MLPA) and single molecular real-time (SMRT) sequencing, as well as Sanger sequencing, to identify variants in five unrelated families with abnormal elevated HbA2 level. All probands in these five families were found to be heterozygous for anti-Lepore Hong Kong. Among them, two families showed co-occurrence of ß0-thalassemia and α-thalassemia (-SEA/ or αCSα/). Heterozygotes for anti-Lepore Hong Kong displayed an average HbA2 level of 17.7% and behaved normal. However, when combined with ß0-thalassemia and α-thalassemia, the probands exhibited higher HbA2 level (30.2-40.8%) and behaved with ß-thalassemia trait. Furthermore, determination of the α/ß-mRNA ratio revealed a slight downregulation of ß-globin, similar to that of ß-thalassemia minor. Our study is the first to identify compound heterozygotes for anti-Lepore Hong Kong, ß0-thalassemia and α-thalassemia, provide valuable information for prenatal counseling.

Selective removal of Hg(II) by chitosan derivative covalently modified with double cross-linking agents abundant in N and S atoms.

With rapid industrialization and urbanization, numerous wastewater contains elevated concentration of Hg(II), and its concentration must be reduced to the discharge limit, so as not to cause serious pollution to the environment. In this paper, a modified chitosan adsorbent material, AMT-DMTD-CS (CS = chitosan, AMT = 2-amino-5-mercapto-1,3,4-thiadiazole, DMTD = 1,3,4-thiadiazole-2,5-dithiol) was prepared. FT-IR, XPS, elemental analysis, and FE-SEM confirmed that AMT and DMTD were successfully grafted covalently onto CS, with BET analysis showing a specific surface area of 105.55 m2/g for AMT-DMTD-CS. Adsorption study suggests that the optimal pH environment for AMT-DMTD-CS to adsorb Hg(II) is 4.0, and the saturated uptake capacity reaches 687.17 mg/g at 318 K, even after eight regenerations, the removal is still maintained at 80.06 %. Moreover, the adsorption behavior is in perfect agreement with the pseudo-second order kinetic model and the Langmuir isotherm model. In addition, AMT-DMTD-CS shows quite favorable selectivity for Hg(II) in a variety of co-existing metal ions. According to the FT-IR and XPS analysis of AMT-DMTD-CS-Hg(II), the synergistic complexation of -OH, -NH2, -NH, CN, CS and -SH to Hg(II) is considered as the main reason that leading to the elevated adsorption capacity.

Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.

An injectable cartilage-coating composite with long-term protection, effective lubrication and chondrocyte nourishment for osteoarthritis treatment.

The osteoarthritic (OA) environment within articular cartilage poses significant challenges, resulting in chondrocyte dysfunction and cartilage matrix degradation. While intra-articular injections of anti-inflammatory drugs, biomaterials, or bioactive agents have demonstrated some effectiveness, they primarily provide temporary relief from OA pain without arresting OA progression. This study presents an injectable cartilage-coating composite, comprising hyaluronic acid and decellularized cartilage matrix integrated with specific linker polymers. It enhances the material retention, protection, and lubrication on the cartilage surface, thereby providing an effective physical barrier against inflammatory factors and reducing the friction and shear force associated with OA joint movement. Moreover, the composite gradually releases nutrients, nourishing OA chondrocytes, aiding in the recovery of cellular function, promoting cartilage-specific matrix production, and mitigating OA progression in a rat model. Overall, this injectable cartilage-coating composite offers promising potential as an effective cell-free treatment for OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) in the articular cartilage leads to chondrocyte dysfunction and cartilage matrix degradation. This study introduces an intra-articular injectable composite material (HDC), composed of decellularized cartilage matrix (dECMs), hyaluronan (HA), and specially designed linker polymers to provide an effective cell-free OA treatment. The linker polymers bind HA and dECMs to form an integrated HDC structure with an enhanced degradation rate, potentially reducing the need for frequent injections and associated trauma. They also enable HDC to specifically coat the cartilage surface, forming a protective and lubricating layer that enhances long-term retention, acts as a barrier against inflammatory factors, and reduces joint movement friction. Furthermore, HDC nourishes OA chondrocytes through gradual nutrient release, aiding cellular function recovery, promoting cartilage-specific matrix production, and mitigating OA progression.

Channel erosion and its impact on environmental flow of riparian habitat in the Middle Yangtze River.

Evaluating environmental flow (EF) is pivotal for conserving and restoring riverine ecosystems. Yet, prevalent EF evaluations presume that a river reach's hydraulic conditions are exclusively governed by inflow discharge, presupposing a state of equilibrium in the river channel. This presumption narrows the scope of EF evaluations in expansive alluvial rivers like the Middle Yangtze River (MYR), characterized by marked channel alterations. Here we show the profound channel erosion process and its impact on EF requirements for riparian habitats within the MYR. Our research unveils that: (i) pronounced erosion has led to a mean reduction of 1.0-2.7 m in the riverbed across four sub-reaches of the MYR; (ii) notwithstanding a 37-107% increase in minimal discharges post the Three Gorges Project, the lowest river stages at some hydrometric stations diminished owing to bed erosion, signifying a notable transformation in MYR's hydraulic dynamics; (iii) a discernible rightward shift in the correlation curve between the weighted useable area and discharge from 2002 to 2020 in a specific sub-reach of the MYR, instigated by alterations in hydraulic conditions, necessitated an increase of 1500-2600 m³ s-1 in the required EF for the sub-reach; (iv) it is deduced that macroinvertebrate biomass rapidly decreases as the flow entrains the riverbed substrate, with the maximum survivable velocity for macroinvertebrates being contingent on their entrainment threshold. These findings highlight the importance of incorporating channel morphological changes in devising conservation strategies for the MYR ecosystem.

Associations between onset age of orthostatic hypotension and incident myocardial infarction, stroke, and dementia: a prospective cohort study.

BACKGROUND: The associations of age at orthostatic hypotension onset with incident myocardial infarction (MI), stroke, and dementia remain unknown. This study aimed to examine whether younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia. METHODS: Data were obtained from the UK Biobank. Information on the diagnosis of orthostatic hypotension, MI, stroke, and dementia was collected at baseline (2006-2010) and follow-ups (median=13 years). The propensity score matching method and the Cox proportional hazard models were employed. RESULTS: A total of 448 374 adults (mean age: 56.8±8.1 years), of whom 3795 had orthostatic hypotension, were included. orthostatic hypotension patients exhibited higher risks of developing MI, stroke, and dementia than non-orthostatic hypotension participants. Importantly, among orthostatic hypotension patients, younger onset age (per 10-year decrement) was significantly associated with high risks of MI (HR=3.15, 95% CI: 2.54 to 3.90, P<0.001), stroke (HR=1.72, 95% CI: 1.33 to 2.23, P<0.001), and dementia (HR=1.26, 95% CI: 1.02 to 1.57, P=0.034). After propensity score matching, orthostatic hypotension patients had significantly higher risks of MI, stroke, and dementia than matched controls among all onset age groups, and the HRs gradually increased with descending onset age. CONCLUSIONS: Younger onset age of orthostatic hypotension was associated with higher risks of incident MI, stroke, and dementia, underscoring the necessity to pay additional attention to the cardiovascular health and neurocognitive status of individuals diagnosed with orthostatic hypotension at younger ages to attenuate subsequent risks of incident cardiovascular diseases and dementia.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

Inhibition of inosine metabolism of the gut microbiota decreases testosterone secretion in the testis.

Growing evidence indicates that gut microbiota is involved in the regulation of the host's sex hormone levels, such as through interfering with the sex hormone metabolism in the intestine. However, if gut microbiota or its metabolites directly influence the sex hormone biosynthesis in the gonad remains largely unknown. Our previous study showed that colistin, as a narrow-spectrum antibiotic, can significantly downregulate the serum testosterone levels and thus enhance the antitumor efficiency of anti-PD-L1 in male mice; however, the underlying mechanism for the regulation of the host's testosterone levels remains uninvestigated. In the present study, we analyzed the impact of colistin on the immune microenvironment of the testis as well as the composition and metabolism of gut microbiota in male mice. Our results showed that colistin has an impact on the immune microenvironment of the testis and can downregulate serum testosterone levels in male mice through inhibition of Akkermansia, leading to destroyed inosine metabolism. Supplement with inosine can restore testosterone secretion probably by prompting the recovery of the intestinal mucus barrier and the serum lipopolysaccharides levels. All these findings reveal a new pathway for the regulation of the host's sex hormone levels by gut microbiota.IMPORTANCEThis study demonstrates that exposure to even narrow-spectrum antibiotics may affect the host's testosterone levels by altering the gut microbiota and its metabolites. Our findings provide evidence that some specific gut bacteria have an impact on the sex hormone biosynthesis in the testis.