A Novel TrxR1 Inhibitor Regulates NK and CD8+ T Cell Infiltration and Cytotoxicity, Enhancing the Efficacy of Anti-PD-1 Immunotherapy against Hepatocarcinoma.

Hepatocellular carcinoma (HCC) has the third highest cancer-related mortality rate globally. The immunosuppressive microenvironment of HCC limits effective treatment options. HCC cells and associated microenvironmental factors suppress NK and T cell infiltration and cytotoxic activities. The abnormal number or function of NK and T cells leads to a lack of immune surveillance. Recently, immunotherapy targeting PD-1 and PD-L1 has been shown to activate functionally exhausted cytotoxic immune cells in some solid tumors. However, the response rate and therapeutic efficacy against solid tumors with little lymphocyte infiltration are limited, especially for HCC. Therefore, new targets and therapeutics that induce tumor cell apoptosis and overcome the problem of depletion of immune cells, thereby inhibiting the immune escape of HCC cells, are urgently required. Butaselen (2-bis[2-(1,2-benzisothiazol-2(2H)-ketone)]butane), an organic molecule containing selenium, is a new type of thioredoxin reductase inhibitor. In this study, we found that butaselen promoted NK and T cell activity and infiltration in the tumor microenvironment in HCC-bearing mice by enhancing the expression of CXCR3, NKG2D, and their respective ligands. When used alone, it can significantly inhibit tumor growth and exert a synergistic effect in combination with PD-1 blockade. We suggested the role of the thioredoxin reductase system in the regulation of the tumor immunosuppressive microenvironment and developed a new effective therapeutic molecule for HCC, revealing the mechanism of butaselen in inhibiting tumor cell immune escape.

Early smoking lead to worse prognosis of COPD patients: a real world study.

BACKGROUND: Smoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity. METHODS: We conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge. RESULTS: Among 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128). CONCLUSION: Early smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.

Errors and Adherence to Inhaled Medications in Chinese Adults with COPD.

BACKGROUND: Adherence to inhaled medications is key to chronic obstructive pulmonary disease (COPD) control and management. OBJECTIVE: To assess errors and adherence to inhalation therapy in COPD patients, and identify potential factors associated with poor adherence. METHODS: This cross-sectional study was conducted from October 1, 2022, to November 30, 2022, in 24 hospital outpatient departments in different cities of Hunan Province, China. Adherence to inhaled medications was measured using the 10-item Test of Adherence Inventory, and the results were expressed using both descriptive and inferential statistics. RESULTS: A total of 2218 clinically confirmed adult COPD patients completed the questionnaires, and 1423 patients with more than a 3-month history of inhalation therapy were analyzed. This study found that 61.3% of patients made one or more use errors. Not holding the breath after inhalation or holding the breath for less than 3 s had the highest reporting rate (30.7%). A considerable proportion of patients (66.6%) demonstrated suboptimal adherence to inhaled medications. Patients who resided in rural areas (OR 1.45, 95% CI 1.12-1.88), used dual therapy (OR 1.47, 95% CI 1.05-2.05), and exhibited common use errors (OR 3.02, 95% CI 2.39-3.82) were more likely to present suboptimal adherence. Patients with CAT (Chronic Obstructive Pulmonary Disease Assessment Test) score < 10 (OR 0.73, 95% CI 0.56-0.94), a junior high school education and above (OR 0.73, 95% CI 0.57-0.94), and duration of inhaled medication use > 3 years (OR 0.63, 95% CI 0.47-0.83) were associated with better adherence. CONCLUSION: Suboptimal adherence to inhaled medications and many inhalation therapy errors were identified among COPD patients. Common use errors in inhaled medications, CAT score, and education background were predictive of and influenced adherence to inhaled medications. It is necessary to strengthen training in Chinese patients about inhaler use and follow-up intensively with patients throughout treatment, especially for patients with risk factors.

Cooperative Cu/Pd-Catalyzed 1,5-Boroacylation of Cyclopropyl-Substituted Alkylidenecyclopropanes.

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B2pin2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

Initial lactate levels linked to oliguria in term neonates with perinatal asphyxia.

BACKGROUND: Oliguria is a sign of impaired kidney function and has been shown to be an early predictor of adverse prognoses in patients with acute kidney injury. The relationship between urine output (UOP) and early lactate levels in neonates with perinatal asphyxia (PA) has not been extensively explored. This study aimed to investigate the link between oliguria during the first 24 h of life and early lactate levels in neonates with PA. METHODS: The medical records of 293 term neonates with asphyxia from 9216 hospitalized newborns were retrospectively analyzed, including 127 cases designated as the oliguria group and 166 cases as controls. Peripheral arterial blood gas after PA and UOP within 24 h after birth were analyzed. Logistic regression analyses and receiver operating characteristic curve analysis were conducted. RESULTS: Oliguria occurred in 43.34% of neonates with PA. The median UOP of the oliguria and control groups were 0.65 and 1.46 mL/kg/h, respectively. Elevated lactate levels after PA are an independent risk factor for oliguria in the following 24 h (p = 0.01; OR: 1.19; 95%CI: 1.04-1.35) and show a moderate discriminatory power for oliguria (AUC = 0.62). Using a cut off value of 8.15 mmol/L, the positive and negative predictive values and the specificity were 59.34%, 63.86%, and 78.30%, respectively. CONCLUSION: Neonates with elevated lactate levels after PA face a risk of oliguria in the following 24 h. Based on early elevated lactate levels after resuscitation, especially ≥ 8.15 mmol/L, meticulously monitoring UOP will allow this vulnerable population to receive early, tailored fluid management and medical intervention.

Dual-mode sensing strategy based on carbon dots for sensitive and selective detection of molybdate ions.

Two kinds of carbon dots with the maximum fluorescence peak of 492 nm (named as G-CDs) and 607 nm (named as R-CDs) were synthesized. In the presence of MoO42- ions, the fluorescence of R-CDs at 607 nm can be quenched, which can probably be assigned to their aggregation caused by MoO42-, while that of G-CDs at 492 nm remained unchanged. For the first time, a ratiometric fluorescence probe was developed for MoO42- ions detection. In the range 0.25 ~ 100 µM, the fluorescence ratio (F492/F607) of the probe was linearly related to MoO42- concentration, and the detection limit was 61.5 nM, which fully meets the minimum detection requirements of MoO42- ions in drinking water. On the other hand, when MoO42- was introduced, a significant fading phenomenon of R-CDs can be observed with the naked eye; thereby, the colorimetric method can also be proposed. Based on above, the ratiometric fluorometric/colorimetric dual-mode sensing method was established for MoO42- anion quantification. Compared with the traditional analysis methods, the results obtained by multimodal sensing can be mutually verified, which effectively improves the accuracy and reliability. The dual-mode assay proposed in this work provides an alternative scheme to meet the need of sensing target compounds in complex matrices.

A theoretical exploration of the structural feature, mechanical, and optoelectronic properties of Au-based halide perovskites A2AuIAuIIIX6 (A = Rb, Cs; X = Cl, Br, I).

As a possible alternative to lead halide perovskites, inorganic mixed-valence Au-based halide perovskites have drawn much attention. In the current research, we have conducted comprehensive theoretical calculations to reveal the structural feature, thermodynamic and dynamic stability, mechanical behavior, optoelectronic properties, and photovoltaic performance of Au-based halide perovskites A2AuIAuIIIX6 (A = Rb, Cs; X = Cl, Br, I). The structural parameters of these compounds are carefully analyzed. Our calculations indicate that the thermodynamic, dynamic, and mechanical stability of monoclinic Rb2AuIAuIIIX6 and tetragonal Cs2AuIAuIIIX6 are ensured, and they are all ductile. The electronic band structure analysis shows that Rb2AuIAuIIII6 illustrates a direct-gap feature, while Rb2AuIAuIIIX6 (X = Cl, Br) and Cs2AuIAuIIIX6 (X = Cl, Br, I) are indirect-gap materials. The effect of A-site cation substitution on the optical band gaps of the Au-based halide perovskites is elucidated. Our results further suggest that Rb2AuIAuIIIX6 (X = Br, I) and Cs2AuIAuIIIX6 (X = Cl, Br, I) are more suitable for single-junction solar cells due to their suitable band gaps within 1.1-1.5 eV. Furthermore, four compounds A2AuIAuIIIX6 (A = Rb, Cs; X = Br, I) not only have high absorption coefficients in the visible region but also show excellent photovoltaic performance, especially for A2AuIAuIIII6 (A = Rb, Cs), whose efficiency can reach over 29% with a film thickness of 0.5 µm. Our study suggests that inorganic Au-based halide perovskites are potential alternatives for optoelectronic devices in solar cells.

Computational study of the fundamental properties of Zr-based chalcogenide perovskites for optoelectronics.

Chalcogenide perovskites have recently attracted enormous attention since they show promising optoelectronic properties and high stability for photovoltaic applications. Herein, the relative stability and photoactive properties of chalcogenide perovskites AZrX3 (A = Ca, Sr, Ba; X = S, Se) including the needle-like (α phase) and distorted perovskite (ß phase) structures are first revealed. The results show that the difference in the relative stability is large between the α and ß phases for both AZrS3 and AZrSe3. The fundamental direct-gap transition is only allowed for the ß phase, which is further confirmed by its optical properties. It is indicated that the suitable direct-gap energy of the α phase is not desirable for thin-film solar cells. Therefore, the stability, and mechanical, electronic, and optical properties of the distorted chalcogenide perovskites AZrS3-xSex (x = 0, 1, 2, 3) are mainly explored for the first time. The predicted direct band gaps of nine compounds AZrS3-xSex (x = 1-3) are in the ideal range of 1.3-1.7 eV. Most compounds have small effective masses, low exciton binding energies, and high optical absorption coefficients in the visible region. Moreover, the mechanical, thermodynamic, and dynamic stabilities are identified for these compounds. Our findings suggest that CaZrSe3, SrZrSe3, and BaZrSe3 are proposed to be the most promising candidates for photovoltaic applications owing to their promising properties.

Absorption, Distribution, Metabolism, and Excretion of [14C]BS1801, a Selenium-Containing Drug Candidate, in Rats.

BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague-Dawley/Long-Evans rats after a single oral dose of 100 mg/kg (100 µCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N-Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801.

Reliability and validity test and application of the Chinese version of the Feeling of Satisfaction with Inhaler. / ä¸­æ–‡ç‰ˆå¸å ¥è¯ç‰©æ»¡æ„åº¦é‡è¡¨çš„ä¿¡æ•ˆåº¦æ£€éªŒåŠåº”ç”¨.

OBJECTIVES: Inhaler satisfaction is an important factor affecting inhaler adherence and the efficacy of inhalers in chronic airway diseases. Using a scientific and effective method to assess patients' satisfaction with inhalers is of great significance for improving clinical outcomes. The Feeling of Satisfaction with Inhaler-10 (FSI-10) is specifically designed to assess patients' inhaler satisfaction in chronic airway diseases, but the application research on this scale is not available in China. This study aims to evaluate the reliability and validity of the Chinese version of FSI-10, describe the current status of inhaler satisfaction and discuss the associated variables in Chinese patients with chronic airway disease. METHODS: Based on the English version of FSI-10, items of the Chinese version of FSI-10 were determined after forward⁃backward translation and cultural adaption. Totally, 322 patients with chronic obstructive pulmonary disease (COPD) and asthma were enrolled from the Second Xiangya Hospital of Central South University from June to October 2022. We collected associated clinical variables and inhaler satisfaction using the Chinese version of FSI-10. The content validity of the scale was expressed by content validity index (CVI) and the construct validity was analyzed by exploratory factor analysis (EFA). The reliability of the scale was expressed by Cronbach's α coefficient, the split-half reliability and test-retest reliability. A multivariate logistic regression was conducted to examine variables related to inhaler satisfaction. RESULTS: The reliability and validity analysis showed that the CVI was 0.983. One factor was extracted from the Chinese version of FSI-10 and the cumulative variance contribution rate was 73.114%. The Cronbach's α of the scale was 0.913, the Guttman's half-reliability coefficient was 0.905, and the test-retest reliability was 0.727 (P<0.001). In addition, the total score of the scale for patients was 38.92±4.26 points and the proportion of high satisfaction (the score of FSI-10≥40) in patients with COPD was significantly lower than that in asthma patients (71.3% vs 87.9%, P<0.01). Older age (age≥70 years) was a risk factor of lower inhaler satisfaction and asthma diagnosis was a protective factor. CONCLUSIONS: The Chinese version of FSI-10 has good reliability and validity in patients with COPD and asthma, which may be further promoted and applied in patients with chronic airway disease in China. Doctors should regularly evaluate the inhaler satisfaction of patients with chronic airway diseases, especially for those elder or with severe symptoms and a long course of illness.

Long noncoding RNA HOTAIR facilitates pulmonary vascular endothelial cell apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD.

BACKGROUND: To study the regulatory effect of Long non-coding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) on pulmonary vascular endothelial cell (HPVEC) apoptosis and determine whether the HOTAIR facilitate HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in chronic obstructive pulmonary disease (COPD). METHODS: LncRNA array was used to measure the differentially expressed lncRNAs in COPD and non-COPD lung tissues. Expression of HOTAIR in COPD patient lungs and cigarette smoke extract (CSE)-induced HPVEC was assessed by qRT-PCR. The location of HOTAIR was determined in COPD patient lungs and HPVEC by RNA in situ hybridization (RNA-ISH). The emphysema mouse model and HOTAIR knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vectors instillation. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cleaved-caspase 3 protein expression were detected by Western blotting. HOTAIR, DNMT1, Bcl-2 and Bax mRNA expression were measured by quantitative real-time polymerase chain reaction. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to assess apoptotic ratio in mice and CSE-induced HPVEC. Methylation-specific PCR (MSP) assay was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. RNA pull-down assay was used for analysis of the correlation between HOTAIR and DNMT1. RESULTS: The expression levels of the HOTAIR were up-regulated in COPD patient lungs and CSE-induced HPVEC. HPVEC apoptosis with down-regulated Bcl-2 expression, increased promoter methylation, DNMT1, Bax and Cleaved-caspase 3 expression was found in emphysema mouse model and CSE-induced HPVEC. Knockdown HOTAIR can attenuate cell apoptosis and emphysema via DNMT1 mediated hypermethylation of Bcl-2 promoter in mice. In vitro, HOTAIR can aggravate the apoptosis of CSE-exposed HPVEC. DNMT1 was a target of HOTAIR and had a positive correlation with HOTAIR. CONCLUSION: HOTAIR facilitates HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD, and attenuating the expression of HOTAIR may be a new therapy to prevent COPD.

Ratiometric Zinc Biosensor Based on Bioluminescence Resonance Energy Transfer: Trace Metal Ion Determination with Tunable Response.

Determination of metal ions such as zinc in solution remains an important task in analytical and biological chemistry. We describe a novel zinc ion biosensing approach using a carbonic anhydrase-Oplophorus luciferase fusion protein that employs bioluminescence resonance energy transfer (BRET) to transduce the level of free zinc as a ratio of emission intensities in the blue and orange portions of the spectrum. In addition to high sensitivity (below nanomolar levels) and selectivity, this approach allows both quantitative determination of "free" zinc ion (also termed "mobile" or "labile") using bioluminescence ratios and determination of the presence of the ion above a threshold simply by the change in color of bioluminescence, without an instrument. The carbonic anhydrase metal ion sensing platform offers well-established flexibility in sensitivity, selectivity, and response kinetics. Finally, bioluminescence labeling has proven an effective approach for molecular imaging in vivo since no exciting light is required; the expressible nature of this sensor offers the prospect of imaging zinc fluxes in vivo.

Potential metal-related strategies for prevention and treatment of COVID-19.

Abstract: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19.

Developmental Consequences of Prenatal Telbivudine Exposure during the Third Trimester.

Hepatitis B virus (HBV) infection is a global health issue. Mother-to-child transmission (MTCT) is the most prominent route for chronic HBV infection in Asian countries.1 Although standard immunoprophylaxis has been effective in preventing MTCT, a significantly higher rate of MTCT has been observed among mothers with high levels of viremia.2 Tenofovir disoproxil, telbivudine (LdT), and lamivudine, used in third trimester, have been shown to significantly reduce MTCT of HBV for highly viremic mothers.3 Although the efficacy and short-term safety of LdT in preventing MTCT have been demonstrated in several large cohort studies in recent years, fewer data exist on the safety assessment of infants' neurocognitive development after fetal exposure to LdT.4-6 Therefore, we conducted a prospective cohort study to investigate the effect of LdT on infants' neurocognitive development.

Simple nomogram based on initial laboratory data for predicting the probability of ICU transfer of COVID-19 patients: Multicenter retrospective study.

This retrospective, multicenter study investigated the risk factors associated with intensive care unit (ICU) admission and transfer in 461 adult patients with confirmed coronavirus disease 2019 (COVID-19) hospitalized from 22 January to 14 March 2020 in Hunan, China. Outcomes of ICU and non-ICU patients were compared, and a simple nomogram for predicting the probability of ICU transfer after hospital admission was developed based on initial laboratory data using a Cox proportional hazards regression model. Differences in laboratory indices were observed between patients admitted to the ICU and those who were not admitted. Several independent predictors of ICU transfer in COVID-19 patients were identified including older age (≥65 years) (hazard ratio [HR] = 4.02), hypertension (HR = 2.65), neutrophil count (HR = 1.11), procalcitonin level (HR = 3.67), prothrombin time (HR = 1.28), and D-dimer level (HR = 1.25). The lymphocyte count and albumin level were negatively associated with mortality (HR = 0.08 and 0.86, respectively). The developed model provides a means for identifying, at hospital admission, the subset of patients with COVID-19 who are at high risk of progression and would require transfer to the ICU within 3 and 7 days after hospitalization. This method of early patient triage allows a more effective allocation of limited medical resources.

Praseodymium selective fluorescence recognition based on GdPO4: Tb3+ probe via energy transfer from Tb3+ to Pr3+ ions.

A novel strategy is proposed based on the efficient energy transfer from Tb3+ to Pr3+ for the sensitive and selective discrimination of praseodymium ions due to the matched energy levels of 5D4 (Tb3+) and 3P0 (Pr3+). The electron of Tb3+ transfers from the ground state to the excited state under the excitation of ultraviolet light and relaxes to the 5D4 level. In the presence of Pr3+ the electron has no time to return to the ground state, thus it transfers to the 3P0 level of Pr3+ resulting in the quenching of Tb3+ luminescence. In the case of GdPO4: Tb3+ nanowire, its fluorescence intensity at 545 nm linearly decreased when Pr3+ concentration ranged from 1 × 10-7 to 1 × 10-5 M, and the detection limit was 75 nM. To further investigate the sensing mechanism, CePO4: Tb3+, YPO4: Tb3+, and YBO3: Tb3+ nanoparticles were also synthesized for Pr3+ ion detection. For all materials, similar fluorescence quenching by Pr3+ ions occurred, which confirmed the efficient energy transfer from Tb3+ to Pr3+ ions. Utilizing the matched energy levels of 5D4 (Tb3+) and 3P0 (Pr3+), for the first time, we proposed a novel strategy (taking GdPO4: Tb3+ probe as the example) based on the efficient energy transfer from Tb3+ to Pr3+ for the sensitive and selective discrimination of praseodymium ions.

Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model.

BACKGROUND: Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are triggered has never been conducted. METHOD: The total reactive oxygen species (ROS) level, pulmonary apoptosis and B-cell lymphoma/leukemia-2 (Bcl-2) expression, an apoptosis regulator, were detected in samples from COPD patients. Bisulfite sequencing PCR (BSP) was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), a vital DNA methyltransferase enzyme, in the lungs of patients was confirmed through western blotting. To find out interactions between oxidative stress and DNA methylation in emphysema, mouse models were built with antioxidant treatment and DNMT1 silencing, and were examined with the pulmonary apoptosis, Bcl-2 and DNMT1 levels, and epigenetic alterations of Bcl-2. RESULTS: Higher ROS levels and pulmonary apoptosis were observed in COPD patients than in healthy controls. Downregulated Bcl-2 expression with increased promoter methylation and DNMT1 protein expression was found in COPD patients. Antioxidant treatment reduced the level of ROS, DNMT1 protein and emphysematous progression in the smoking models. Following DNMT1 blockade, smoking models showed improved lung function, pulmonary apoptosis, emphysematous progression, and increased Bcl-2 protein level with less promoter methylation than emphysema mice. CONCLUSION: Cigarette-induced oxidative stress mediates pulmonary apoptosis and hypermethylation of the Bcl-2 promoter in emphysema models through DNMT1.

Perinatal listeriosis patients treated at a maternity hospital in Beijing, China, from 2013-2018.

BACKGROUND: Listeriosis is a rare but severe foodborne infectious disease. Perinatal listeriosis is often associated with septicemia, central nervous system (CNS) infection, and serious adverse pregnancy outcomes (miscarriage and neonate death). Here we report the characteristics and outcomes of perinatal listeriosis cases treated over 6 years at Beijing Obstetrics and Gynecology Hospital (BOGH), the largest maternity hospital in China. METHODS: We retrospectively reviewed the records of laboratory-confirmed, pregnancy-associated listeriosis cases treated from January 1, 2013 to December 31, 2018. The clinical manifestations, laboratory results, perinatal complications and outcomes (post-natal follow-up of 6 months) were investigated. RESULTS: In BOGH, 12 perinatal listeriosis cases were diagnosed based on Listeria monocytogenes positive culture, including 10 single pregnancies and 2 twin pregnancies. The corresponding incidence of pregnancy-associated listeriosis was 13.7/100,000 deliveries. Among those cases, four pregnant women and four newborns had septicemia, and two of the neonates with septicemia also suffered CNS infection. All the maternal patients recovered. Two inevitable miscarriages and four fetal stillbirths occurred. Of the eight delivered newborns, six survived, and two died within 2 days from birth. None of the survivors had neurological sequelae during a 6-month follow-up. The overall feto-neonatal fatality rate was 57.1%; notably, this rate was 100% for infections occurring during the second trimester of pregnancy and only 14.3% for those occurring in the third trimester. CONCLUSIONS: Perinatal listeriosis is associated with high feto-neonatal mortality, and thus, a public health concern. Additional large-scale studies are needed to strengthen the epidemiological understanding of listeriosis in China.

Effects of a formula with a probiotic Bifidobacterium lactis Supplement on the gut microbiota of low birth weight infants.

PURPOSE: Low birth weight (LBW) infants have a less diverse gut microbiota, enriched in potential pathogens, which places them at high risk of systemic inflammation diseases. This study aimed to identify the differences in gut bacterial community structure between LBW infants who received probiotics and LBW infants who did not receive probiotics. METHODS: Forty-one infants were allocated to the non-probiotic group (N group) and 56 infants to the probiotic group (P group), according to whether the formula they received contained a probiotic Bifidobacterium lactis. Gut bacterial composition was identified with sequencing of the 16S rRNA gene in fecal samples collected at 14 days after birth. RESULTS: There was no significant difference between the alpha diversity of the two groups, while the beta diversity was significantly different (p < 0.05). Our results showed that Bifidobacterium and Lactobacillus (both p < 0.05) were enriched in the P group, while Veillonella, Dolosigranulum and Clostridium sensu stricto 1 (all p < 0.05) were enriched in the N group. Predicted metagenome function analysis revealed enhancement of fatty acids, peroxisome, starch, alanine, tyrosine and peroxisome pathways in the P group, and enhancement of plant pathogen, Salmonella and Helicobacter pylori infection pathways in the N group. CONCLUSIONS: Probiotic supplement in formula may affect the composition, stability and function of LBW infants' gut microbiota. LBW infants who receive probiotic intervention may benefit from gut microbiota that contains more beneficial bacteria.

Blood and Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pneumonia.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has made a revolution in the mode of pathogen identification. We decided to explore the diagnostic value of blood and bronchoalveolar lavage fluid (BALF) as mNGS samples in pneumonia. METHODS: We retrospectively reviewed 467 mNGS results and assessed the diagnostic performance of paired blood and BALF mNGS in 39 patients with pneumonia. RESULTS: For bacteria and fungi, 16 patients had culture-confirmed pathogen diagnosis, while 13 patients were culture-negative. BALF mNGS was more sensitive than blood mNGS (81.3% vs. 25.0%, p=0.003), and the specificity in BALF and blood mNGS was not statistically significant different (76.9% vs. 84.6%, p=0.317). For 10 patients without culture test, treatments were changed in 2 patients. For viruses, Epstein-Barr virus was positive in blood mNGS in 9 patients. Human adenovirus was detected in both BALF and blood mNGS in 3 patients. CONCLUSION: Our study suggests that BALF mNGS is more sensitive than blood mNGS in detecting bacteria and fungi, but blood also has advantages to identify the pathogens of pneumonia, especially for some viruses.