Highly diverse sputum microbiota correlates with the disease severity in patients with community-acquired pneumonia: a longitudinal cohort study.

BACKGROUND: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. METHODS: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. RESULTS: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. CONCLUSION: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.

Apolipoprotein C3 is negatively associated with estrogen and mediates the protective effect of estrogen on hypertriglyceridemia in obese adults.

BACKGROUND: Both estrogen and apolipoprotein C3 (ApoC3) play crucial roles in lipid metabolism. But the link between them remains unclear, and it is unknown whether estrogen regulates triglyceride (TG) levels via ApoC3. Researchers hypothesized that estrogen exerts a regulatory effect on ApoC3 metabolism, and that this regulation could play a significant role in lipid metabolism. To explore this potential link, the present investigation aimed to examine the associations between estradiol (E2), ApoC3, and TG levels in both males and females. METHODS: A total of 519 obese people (133 males and 386 premenopausal females) were recruited. Based on their TG levels, the participants were split into two groups [hypertriglyceridemia (HTG) group: TG ≥ 1.7 mmol/L; control group: TG < 1.7 mmol/L]. Serum ApoC3, E2, and TG levels were measured and compared in those two groups for both sexes separately. To ascertain the connection among E2, ApoC3, and TG, linear regression and mediation analysis were used. RESULTS: Participants in the HTG group presented higher levels of ApoC3 (P < 0.001). In contrast, they tend to have lower E2 levels than the control. Linear regression analysis proposed that in both sexes, E2 was negatively associated with ApoC3 levels. The relationship remained significant after adjustment for confounding factors (male: standardized ß = -0.144, t = -2.392, P < 0.05; female: standardized ß = -0.077, t = -2.360, P < 0.001). Furthermore, mediation analysis revealed the relationship between reduced E2 levels and elevated TG levels is directly mediated by ApoC3. CONCLUSIONS: In obese men and premenopausal women, ApoC3 was negatively and linearly correlated with serum E2 levels. The findings showed that estrogen may suppress ApoC3 expression and thus lower TG levels.

miR-155-1 as a positive factor for novel duck reovirus replication by regulating SOCS5-mediated interferons.

Diseases caused by novel duck reovirus (NDRV) have brought considerable economic losses to the poultry industry. MicroRNAs (miRNAs) have an impact on virus replication and antiviral immunity. However, the miRNA profile upon NDRV infection in duck embryo fibroblasts (DEFs) remains to be discovered. In this study, small RNA (sRNA) sequencing was performed to decipher the cellular miRNA response to NDRV infection. Based on 26 differentially expressed miRNAs (19 upregulated and 7 downregulated miRNAs) obtained from sequencing data and their target genes predicted by software, GO and KEGG analyses were performed to elucidate the functions of miRNAs in NDRV invasion, replication, and virus spread. "FoxO signaling pathway", "autophagy", and "Toll-like receptor signaling pathway" might participate in NDRV replication as revealed by KEGG enrichment analysis. The miR-155-1 sequence was found to be identical to rno-miR-155-5p and was sharply increased with the progression of NDRV infection. Moreover, NDRV-induced miR-155-1 could act as a positive factor for virus replication in DEFs, which inhibited type I interferon (IFN-I) production. Luciferase assay confirmed that miR-155-1 disturbed the abundance of suppressor of cytokine signaling (SOCS) 5 by targeting 3'-UTR. SOCS5, which is linked to increased IRF7 expression, restricts IFN expression and promotes NDRV replication in DEFs. Therefore, this study proposed that miR-155-1 was used by NDRV to restrict SOCS5 expression, attenuating the production of IFN-I and creating a favorable environment for virus replication.

Pregnancy outcomes and risk factors for preeclampsia in dichorionic twin pregnancies after in vitro fertilization: a five-year retrospective study.

BACKGROUND: Both in vitro fertilization (IVF) and preeclampsia (PE) were associated with placental dysfunction. Although IVF can increase the incidence of PE, the pregnancy outcomes and risk factors for preeclampsia in dichorionic twin pregnancies conceived via IVF remain unclear. This study aimed to investigate the pregnancy outcomes and the risk factors for preeclampsia in dichorionic twin pregnancies conceived through IVF compared to those conceived after natural conception (NC). METHODS: This retrospective observational study enrolled 181 dichorionic twin pregnancy women with preeclampsia from 2016 to 2020. According to the mode of conception, they were allocated into IVF (n = 117) and NC groups (n = 64). The clinical characteristics of preeclampsia and pregnancy outcomes between the two groups were compared by using Student's t test, chi-square test, and Fisher's exact test, and logistic regression models were used to obtain adjusted odds ratios (aOR) with 95% confidence intervals (CI) for risk factors of early-onset preeclampsia. RESULTS: The incidence of early-onset PE and growth discordance in dichorionic twin pregnancies with PE is significantly higher in IVF-PE group than in NC group (78.60% vs 43.80%, P < 0.001, 11.10% vs 25.00%, P = 0.015). We found that IVF (aOR = 4.635, 95% CI: 2.130-10.084, P < 0.001) and growth discordance (aOR = 3.288; 95% CI: 1.090-9.749, P < 0.05) increased the incidence of early-onset PE. CONCLUSIONS: In preeclamptic dichorionic twin pregnancies, IVF and growth discordance were associated with the increased incidence of early-onset PE. The underlying mechanism for the relationship between IVF and early-onset PE or growth discordance may be placental dysfunction.

Study on the relationship between hormone and Lp(a) in Chinese overweight/obese patients.

BACKGROUND: Obesity is a risk factor for metabolic diseases and often influences hormone change. Lipoprotein (a) (Lp(a)) is associated with various metabolic diseases, but there are few studies on the relationship between Lp(a) and hormones in obese patients. This study investigated the the relationship between Lp(a) and hormones in Chinese overweight/obese people. METHODS: A total of 410 overweight/obese patients (Body mass index (BMI) ≥ 25 kg/m2) were included and underwent sociodemographic data investigations and relevant clinical examinations. Lp(a) was analyzed by colorimetric enzymatic assays and hormone was measured with chemiluminescence immunoassay method. According to Lp(a) levels, they were categorized into 3 groups: the lower Lp(a) group (Lp(a) levels < 30 mg/dl), the moderate Lp(a) group (Lp(a) levels between 30 mg/dl and 120 mg/dl) and the higher Lp(a) group (Lp(a) levels > 120 mg/dl). The differences of hormone levels among the three groups were compared and the relationship between Lp(a) and hormones was analyzed by Spearman's rank correlation. RESULTS: The higher Lp(a) group had significantly lower testosterone (TES) levels compared with the lower and moderate Lp(a) groups in the case of gender, age and BMI matching. Lp(a) concentration was negatively correlated with TES levels in all participants and the negative association between Lp(a) and TES levels was also observed when the analysis was stratified by gender. Additionally, the TES was statistically related with Lp(a) levels in the multiple linear regression model (95% confidence interval: - 0.451 to - 0.079). CONCLUSIONS: TES levels was negatively associated with Lp(a) levels in Chinese overweight/obese patients.

Chronic toxicity effects of sediment-associated polystyrene nanoplastics alone and in combination with cadmium on a keystone benthic species Bellamya aeruginosa.

Nanoplastics (NPs) are emerging pollutants that may adversely affect aquatic fauna. However, the adverse effects of NPs and heavy metals, both alone and combined on freshwater benthic fauna remain largely unclear. Here, we performed a 28-day sediment toxicity test with Bellamya aeruginosa to examine the effects of exposure to polystyrene nanoplastics (PSNPs) and co-exposure to PSNPs and Cd. Cd bioavailability, the bioaccumulation of PSNPs and Cd, and changes in multiple biomarkers were determined. The results revealed that PSNPs significantly increased Cd bioavailability and thereby facilitated Cd bioaccumulation; however, PSNPs displayed a negligible vector role in Cd uptake by B. aeruginosa. The results demonstrated that PSNPs can accumulate in B. aeruginosa and induce oxidative damage and DNA damage. Co-exposure to PSNPs and Cd significantly enhanced oxidative damage and DNA damage and reduced metallothionein levels. The integrated biomarker response index analysis showed that co-exposure to PSNPs and Cd considerably increased toxic stress in B. aeruginosa compared to single PSNPs or Cd exposure, suggesting that PSNPs may have a synergistic effect with Cd. Collectively, our findings highlight that PSNPs not only cause toxicity to B. aeruginosa but also significantly enhance the toxicity of Cd by increasing Cd bioavailability in the sediment.

An engineered genetic circuit for lactose intolerance alleviation.

BACKGROUND: Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal ß-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal ß-galactosidase activity and influence intestinal homeostasis. RESULTS: Here, we synthesized a tri-stable-switch circuit equipped with high ß-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of ß-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and ß-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. CONCLUSIONS: Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain ß-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.

Effects of the leaf functional traits of coniferous and broadleaved trees in subtropical monsoon regions on PM2.5 dry deposition velocities.

Plants can intercept airborne particulate matter through deposition. Different types of plants exhibit different functional leaf traits, which can affect the dry deposition velocity (Vd). However, the most crucial leaf traits of coniferous and broadleaved trees remain unidentified. In this study, we selected 18 typical plants from the subtropical monsoon regions, where PM2.5 (fine particulate matter with a diameter of ≤2.5 µm) concentrations are relatively high, and classified them into coniferous and broadleaved categories. Subsequently, we analyzed the relationships between Vd and leaf surface free energy (SFE), single leaf area (LAs), surface roughness (SR), specific leaf area (SLA), epicuticular wax content (EWC), and width-to-length ratio (W/L). The results indicated that most coniferous trees exhibited a high Vd. The correlation analysis revealed that SFE, SR, LAs, and W/L were the key factors that affected the Vd of all the tested species. SFE and SLA had the strongest influence on the Vd of broadleaved trees, whereas LAs and SLA had the strongest effect on that of coniferous trees. Most coniferous trees had a high SLA, which can reduce water loss and hinder particle deposition. However, the stiff leaves of coniferous trees fluttered less, resulting in a larger leaf area that enhanced the capture efficiency. The leaf structure of broadleaved trees is more flexible, resulting in erratic flutter, which may impede deposition and lead to high resuspension. Coniferous and broadleaved trees may have different dominant leaf traits that affect particle deposition.

Classification of the Gut Microbiota of Patients in Intensive Care Units During Development of Sepsis and Septic Shock.

The gut microbiota of intensive care unit (ICU) patients displays extreme dysbiosis associated with increased susceptibility to organ failure, sepsis, and septic shock. However, such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota. We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis. We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions. During the development of sepsis or septic shock and during various medical treatments, the ICU patients always exhibited two dysbiotic microbiota patterns, or ICU-enterotypes, which could not be explained by host properties such as age, sex, and body mass index, or external stressors such as infection site and antibiotic use. ICU-enterotype I (ICU E1) comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae, while ICU-enterotype II (ICU E2) comprised predominantly Enterococcus. Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores > 18, septic shock was more likely to occur with ICU E1 (P = 0.041). Additionally, ICU E1 was correlated with high serum lactate levels (P = 0.007). Therefore, different patterns of dysbiosis were correlated with different clinical outcomes, suggesting that ICU-enterotypes should be diagnosed as independent clinical indices. Thus, the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients. This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.

Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin.

Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.