Effect of prone positioning ventilation on pulmonary function in neonates during venous-arterial extracorporeal membrane oxygenation.

Background: The use of extracorporeal membrane oxygenation (ECMO) technology has significantly decreased mortality rates associated with neonatal pulmonary hypertension and respiratory failure. Prone positioning ventilation (PPV) is a commonly used technique in critically ill infants, designed to improve thoracic pressure gradients, re-expand dorsal lung segments, and increase oxygenation in approximately 70-80% of patients suffering from acute respiratory distress syndrome. This study aimed to evaluate the effects of PPV on pulmonary function in neonates undergoing venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: We conducted a retrospective analysis of clinical data from 17 neonates who received ECMO support in our institution, divided into two groups based on ventilation strategy: ECMO with PPV (ECMO-PPV, n=8) and ECMO with supine positioning ventilation (ECMO-SPV, n=9). Parameters such as the P/F ratio [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2)], oxygenation index (OI), respiratory system compliance (Crs), and airway resistance (RAW) were collected and analyzed at baseline, and at 1, 2, and 3 days post-ECMO initiation. In the ECMO-PPV group, these parameters were also assessed 3 days pre-treatment and 2 hours post-treatment initiation. Results: Initial comparisons between ECMO-PPV and ECMO-SPV groups showed no significant difference in PaO2/FiO2, OI, Crs, or RAW. Throughout the ECMO treatment, both groups demonstrated gradual improvements in PaO2/FiO2 and Crs, and reductions in OI and RAW. Notably, by day 3, the ECMO-PPV group exhibited significant improvements in Crs and RAW compared to the ECMO-SPV group (P<0.05). Specifically, in the ECMO-PPV group, Crs significantly increased and RAW decreased after 2 hours of initiating PPV, with these changes becoming statistically significant by day 3 (Crs P=0.03, RAW P=0.03). No severe PPV-related complications were noted. Conclusions: PPV during neonatal ECMO may improve respiratory compliance and reduce RAW, potentially aiding lung recovery. Our findings suggest PPV as a viable strategy for neonates under ECMO support.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

IFI30 as a key regulator of PDL1 immunotherapy prognosis in breast cancer.

BACKGROUND: IFI30 is a lysosomal thiol reductase involved in antigen presentation and immune regulation in various cancers, including breast cancer. Despite its known involvement, the precise mechanism, function, and relationship with the PD-L1 axis and immune response remain unclear. METHODS: We conducted an extensive investigation into IFI30 mRNA expression in breast cancer utilizing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Furthermore, we characterized IFI30 mRNA expression across various cell types using publicly available single-cell RNA sequencing datasets, and assessed protein expression through immunohistochemistry using an in-house breast cancer tissue microarray. Functional experiments were performed to elucidate the effects of IFI30 overexpression on PD-L1 expression and inhibitory efficacy in both macrophages and breast tumor cells. RESULTS: Our study unveiled a marked upregulation of IFI30 expression in breast cancer tissues compared to their normal counterparts, with notable associations identified with tumor stage and prognosis. Additionally, IFI30 expression demonstrated significant correlations with various immune-related signaling pathways, encompassing peptide antigen binding, cytokine binding, and MHC class II presentation. Notably, breast cancer samples exhibiting high IFI30 expression in tumor cells displayed high PD-L1 expression on corresponding cells, alongside a diminished ratio of CD8 + T cell infiltration within the tumor microenvironment. Furthermore, ectopic knockdown of IFI30 in both tumor cells and macrophages resulted in a reduction of PD-L1 expression, while conversely, overexpression of IFI30 led to an increase in PD-L1 expression. CONCLUSIONS: This study offers new insights into the involvement of IFI30 in breast cancer, elucidating its interplay with the PD-L1 axis and immune response dynamics. Our findings suggest that modulation of the IFI30-PD-L1 axis could serve as a promising strategy for regulating T cells infiltration in breast cancer thus treating breast cancer.

Phytoplankton-derived polysaccharides and microbial peptidoglycans are key nutrients for deep-sea microbes in the Mariana Trench.

BACKGROUND: The deep sea represents the largest marine ecosystem, driving global-scale biogeochemical cycles. Microorganisms are the most abundant biological entities and play a vital role in the cycling of organic matter in such ecosystems. The primary food source for abyssal biota is the sedimentation of particulate organic polymers. However, our knowledge of the specific biopolymers available to deep-sea microbes remains largely incomplete. One crucial rate-limiting step in organic matter cycling is the depolymerization of particulate organic polymers facilitated by extracellular enzymes (EEs). Therefore, the investigation of active EEs and the microbes responsible for their production is a top priority to better understand the key nutrient sources for deep-sea microbes. RESULTS: In this study, we conducted analyses of extracellular enzymatic activities (EEAs), metagenomics, and metatranscriptomics from seawater samples of 50-9305 m from the Mariana Trench. While a diverse array of microbial groups was identified throughout the water column, only a few exhibited high levels of transcriptional activities. Notably, microbial populations actively transcribing EE genes involved in biopolymer processing in the abyssopelagic (4700 m) and hadopelagic zones (9305 m) were primarily associated with the class Actinobacteria. These microbes actively transcribed genes coding for enzymes such as cutinase, laccase, and xyloglucanase which are capable of degrading phytoplankton polysaccharides as well as GH23 peptidoglycan lyases and M23 peptidases which have the capacity to break down peptidoglycan. Consequently, corresponding enzyme activities including glycosidases, esterase, and peptidases can be detected in the deep ocean. Furthermore, cell-specific EEAs increased at 9305 m compared to 4700 m, indicating extracellular enzymes play a more significant role in nutrient cycling in the deeper regions of the Mariana Trench. CONCLUSIONS: Transcriptomic analyses have shed light on the predominant microbial population actively participating in organic matter cycling in the deep-sea environment of the Mariana Trench. The categories of active EEs suggest that the complex phytoplankton polysaccharides (e.g., cutin, lignin, and hemicellulose) and microbial peptidoglycans serve as the primary nutrient sources available to deep-sea microbes. The high cell-specific EEA observed in the hadal zone underscores the robust polymer-degrading capacities of hadal microbes even in the face of the challenging conditions they encounter in this extreme environment. These findings provide valuable new insights into the sources of nutrition, the key microbes, and the EEs crucial for biopolymer degradation in the deep seawater of the Mariana Trench. Video Abstract.

Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Patient mistreatment, social sharing of negative events and emotional exhaustion among Chinese nurses: the combined moderating effect of organizational support and trait resilience.

BACKGROUND: As a primary form of work-related violence in the healthcare sector, patient mistreatment negatively impacts nurses' well-being. To date, there has yet reached a definitive conclusion on the mediating mechanism and boundary conditions behind the influence of patient mistreatment on nurses' emotional exhaustion. METHODS: This study employed a convenience sampling method to recruit a sample of 1672 nurses from public hospitals in Western China. The data were collected through anonymous self-report questionnaires and analyzed using hierarchical regression and conditional processes to investigate a theoretical framework encompassing patient mistreatment, emotional exhaustion, social sharing of negative events, organizational support, and trait resilience. RESULTS: Patient mistreatment led to emotional exhaustion among nurses (ß = 0.625, p <.001), and social sharing of negative events mediated this positive relationship (effect = 0.073, SE = 0.013). The combined effects of organizational support and resilience moderated the mediating effect of the social sharing of negative events between patient mistreatment and emotional exhaustion (ß=-0.051, p <.05). Specifically, nurses with a high level of resilience would benefit from organizational support to alleviate emotional exhaustion caused by patient mistreatment. CONCLUSIONS: This study validated a significant positive association between patient mistreatment and emotional exhaustion, which aligns with previous research findings. Integrating conservation of resources theory and goal progress theory, we addressed previous contradictory findings on the impact of social sharing of negative events on emotional exhaustion. Social sharing of negative events served as a mediator between patient mistreatment and emotional exhaustion. Additionally, the moderating effect of organizational support on the relationship between social sharing of negative events and emotional exhaustion depended on individual trait of resilience.

Development of an attenuated potato virus Y mutant carrying multiple mutations in helper-component protease for cross-protection.

Tobacco (Nicotiana tabacum) is one of the major cash crops in China. Potato virus Y (PVY), a representative member of the genus Potyvirus, greatly reduces the quality and yield of tobacco leaves by inducing veinal necrosis. Mild strain-mediated cross-protection is an attractive method of controlling diseases caused by PVY. Currently, there is a lack of effective and stable attenuated PVY mutants. Potyviral helper component-protease (HC-Pro) is a likely target for the development of mild strains. Our previous studies showed that the residues lysine at positions 124 and 182 (K124 and K182) in HC-Pro were involved in PVY virulence, and the conserved KITC motif in HC-Pro was involved in aphid transmission. In this study, to improve the stability of PVY mild strains, K at position 50 (K50) in KITC motif, K124, and K182 were separately substituted with glutamic acid (E), leucine (L), and arginine (R), resulting in a triple-mutant PVY-HCELR. The mutant PVY-HCELR had attenuated virulence and did not induce leaf veinal necrosis symptoms in tobacco plants and could not be transmitted by Myzus persicae. Furthermore, PVY-HCELR mutant was genetically stable after six serial passages, and only caused mild mosaic symptoms in tobacco plants even at 90 days post inoculation. The tobacco plants cross-protected by PVY-HCELR mutant showed high resistance to the wild-type PVY. This study showed that PVY-HCELR mutant was a promising mild mutant for cross-protection to control PVY.

Single-Lung Ventilation in Infants for Surgical Repair of Coarctation of The Aorta Without Cardiopulmonary Bypass.

OBJECTIVE: To investigate the effect of improving the operative field and postoperative atelectasis of single-lung ventilation (SLV) in the surgical repair of coarctation of the aorta (CoA) in infants without the use of cardiopulmonary bypass (CPB). METHODS: This was a retrospective cohort study. The clinical data of 28 infants (aged 1 to 4 months, weighing between 4.2 and 6 kg) who underwent surgical repair of CoA without CPB from January 2019 to May 2022 were analyzed. Fourteen infants received SLV with a bronchial blocker (Group S), and the other 14 infants received routine endotracheal intubation and bilateral lung ventilation (Group R). RESULTS: In comparison to Group R, Group S exhibited improved exposure of the operative field, a lower postoperative atelectasis score (P<0.001), reduced prevalence of hypoxemia (P=0.01), and shorter durations of operation, mechanical ventilation, and ICU stay (P=0.01, P<0.001, P=0.03). There was no difference in preoperative information or perioperative respiratory and circulatory indicators before SLV, 10 minutes after SLV, and 10 minutes after the end of SLV between the two groups (P>0.05). Intraoperative bleeding, intraoperative positive end-expiratory pressure (PEEP), and systolic pressure gradient across the coarctation after operation were also not different between the two groups (P>0.05). CONCLUSION: This study demonstrates that employing SLV with a bronchial blocker is consistent with enhanced operative field, reduced operation duration, lower prevalence of intraoperative hypoxemia, and fewer postoperative complications during the surgical repair of CoA in infants without the use of CPB.

Toxic Potencies of Particulate Matter from Typical Industrial Plants Mediated with Acidity via Metal Dissolution.

Acidity is an important property of particulate matter (PM) in the atmosphere, but its association with PM toxicity remains unclear. Here, this study quantitively reports the effect of the acidity level on PM toxicity via pH-control experiments and cellular analysis. Oxidative stress and cytotoxicity potencies of acidified PM samples at pH of 1-2 were up to 2.8-5.2 and 2.1-13.2 times higher than those at pH of 8-11, respectively. The toxic potencies of PM samples from real-world smoke plumes at the pH of 2.3 were 9.1-18.2 times greater than those at the pH of 5.6, demonstrating a trend similar to that of acidified PM samples. Furthermore, the impact of acidity on PM toxicity was manifested by promoting metal dissolution. The dramatic increase by 2-3 orders of magnitude in water-soluble metal content dominated the variation in PM toxicity. The significant correlation between sulfate, the pH value, water-soluble Fe, IC20, and EC1.5 (p < 0.05) suggested that acidic sulfate could enhance toxic potencies by dissolving insoluble metals. The findings uncover the superficial association between sulfate and adverse health outcomes in epidemiological research and highlight the control of wet smoke plume emissions to mitigate the toxicity effects of acidity.

Microglial SCAP deficiency protects against diabetes-associated cognitive impairment through inhibiting NLRP3 inflammasome-mediated neuroinflammation.

Hyperglycemia-induced pathological microglial responses and subsequent neuronal damage are notable characteristics of diabetes-associated cognitive impairment (DACI). Cholesterol accumulation in the brain is a prevalent consequence of diabetes mellitus (DM), exacerbating pathological microglial responses. Regarding disordered glucose and lipid metabolism, the Sterol Regulatory Element-Binding Protein (SREBP) cleavage-activating protein (SCAP), a cholesterol sensor, exhibits increased expression and abnormal translocation from the endoplasmic reticulum to the Golgi, amplifying the inflammatory response. Therefore, we hypothesized that overexpression of microglia-SCAP and cholesterol accumulation in DM mice could induce pathological microglial responses associated with DACI. Our type 2 DM mice model presented an abnormal increase in microglial SCAP expression. The functional loss of microglia-specific SCAP in DM mice improved cognitive impairment, neuronal synaptic plasticity deficits, and abnormal microglial responses. Mechanistically, the accumulated SCAP directly bound to and enhanced the activation of the microglial-specific inflammatory amplifier, NLRP3 inflammasome, in Golgi, thereby increasing pathological microglial responses and promoting neuronal damage. These findings indicate an important regulatory axis of microglial responses from SCAP to the NLRP3 inflammasome pathway in microglia. These underscore the crosstalk between cholesterol disorders and pathological microglial responses, offering a promising avenue for pharmaceutical interventions in DACI.

Maternal cardiovascular health in early pregnancy and the risk of congenital heart defects in offspring.

BACKGROUND: Congenital heart disease (CHD) is the predominant birth defect. This study aimed to explore the association between maternal cardiovascular health (CVH) and the CHD risk in offspring. METHODS: We used the prospective data from the Fujian Birth Cohort Study, collected from March 2019 to December 2022 on pregnant women within 14 weeks of gestation. Overall maternal CVH was assessed by seven CVH metrics (including physical activity, smoking, sleep duration, body mass index, blood pressure, total cholesterol, and fasting plasma glucose), with each metric classified as ideal, intermediate or poor with specific points. Participants were further allocated into high, moderate and low CVH categories based on the cumulative CVH score. The association with offspring CHD was determined with log-binominal regression models. RESULTS: A total of 19810 participants aged 29.7 (SD: 3.9) years were included, with 7846 (39.6%) classified as having high CVH, 10949 (55.3%) as having moderate CVH, and 1015 (5.1%) as having low CVH. The average offspring CHD rate was 2.52%, with rates of 2.35%, 2.52% and 3.84% across the high, moderate and low CVH categories, respectively (P = 0.02). Adjusted relative risks (RRs) of having offspring CHD were 0.64 (95% CI: 0.45-0.90, P = 0.001) for high CVH and 0.67 (95% CI: 0.48-0.93, P = 0.02) for moderate CVH compared to low CVH. For individual metrics, only ideal total cholesterol was significantly associated with lower offspring CHD (RR: 0.73, 95% CI: 0.59-0.83, P = 0.002). CONCLUSIONS: Pregnant women of high or moderate CVH categories in early pregnancy had reduced risks of CHD in offspring, compared to those of low CVH. It is important to monitor and improve CVH during pre-pregnancy counseling and early prenatal care.

Exploring brain network oscillations during seizures in drug-naïve patients with juvenile absence epilepsy.

Objective: We aimed to investigate the brain network activity during seizures in patients with untreated juvenile absence epilepsy. Methods: Thirty-six juvenile absence epilepsy (JAE) patients with a current high frequency of seizures (more than five seizures during a 2 h EEG examination) were included. Each participant underwent a 2 h video EEG examination. Five 10 s EEG epochs for inter-ictal, pre-ictal, and post-ictal, and five 5 s EEG epochs for ictal states were extracted. Five 10 s resting-state EEG epochs for each participant from a sex- and age-matched healthy control (HC) were enrolled. The topological parameters of the brain networks were calculated using a graph theory analysis. Results: Compared with the resting state of the HC group, the global efficiency, local efficiency, and clustering coefficients of the JAE group decreased in the inter-ictal state. In addition, the ictal state showed significantly increased global and local efficiency and clustering coefficients (p < 0.05) and a decreased small-world index and the shortest path length (p < 0.05) in the theta and alpha bands, compared to the remaining states within the JAE group. Moreover, subgroup analysis revealed that those JAE patients with typical 3 Hz discharges had upgraded global efficiency, local efficiency, and clustering coefficients in both delta and beta1 bands, compared to those JAE patients with non-3 Hz discharges during seizures. Conclusion: The present study supported the idea that the changes in the EEG brain networks in JAE patients are characterized by decreased global and local efficiency and clustering coefficient in the alpha band. Moreover, the onset of seizures is accompanied by excessively enhanced network efficiency. JAE patients with different ictal discharge patterns may have different functional network oscillations.

ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC's ATPase Activity.

Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including Mycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed by M. smegmatis against COG1410 involving ClpC. Upon subjecting M. smegmatis to serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance.

Relationship between heart failure and intestinal inflammation in infants with congenital heart disease.

OBJECTIVE: The association between heart failure (HF) and intestinal inflammation caused by a disturbed intestinal microbiota in infants with congenital heart disease (CHD) was investigated. METHODS: Twenty infants with HF and CHD who were admitted to our hospital between October 2021 and March 2022 were included in this study. Twenty age- and sex-matched infants without HF at our hospital were selected as the control group. Faecal samples were obtained from each participant and analysed by enzyme-linked immunoassay and 16 S rDNA sequencing to assess intestinal inflammatory factors and the microbiota. RESULTS: The levels of intestinal inflammatory factors, including IL-1ß, IL-4, IL-6, IL-17 A and TNF-α, were greatly increased, while the levels of IL-10 were significantly decreased in the HF group compared to the control group (p < 0.05). The intestinal microbial diversity of patients in the HF group was markedly lower than that in the control group (p < 0.05). The abundance of Enterococcus was significantly increased in the HF group compared to the control group (p < 0.05), but the abundance of Bifidobacterium was significantly decreased in the HF group compared to the control group (p < 0.05). The diversity of the intestinal microbiota was negatively correlated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was positively correlated with that of IL-10. The abundance of Enterococcus was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the intestinal tract but was negatively correlated with that of IL-10. NT-proBNP was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. The heart function score was positively associated with the levels of IL-1ß, IL-4, IL-6 and TNF-α in the HF group but was negatively correlated with that of IL-10. CONCLUSIONS: Infants with CHD-related HF had a disordered intestinal microbiota, decreased diversity of intestinal microbes, increased levels of pathogenic bacteria and decreased levels of beneficial bacteria. The increased abundance of Enterococcus and the significant decrease in the diversity of the intestinal microbiota may exacerbate the intestinal inflammatory response, which may be associated with the progression of HF.

Architecture of symbiotic dinoflagellate photosystem I-light-harvesting supercomplex in Symbiodinium.

Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI-AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI-AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI-AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI-LHCI among various photosynthetic organisms.

Application value of metagenomics next-generation sequencing in the diagnosis of respiratory virus infection after congenital heart surgery.

Background: Timely and accurate pathogen diagnosis can be challenging in children who contract a respiratory virus following congenital heart surgery (CHS). This often results in suboptimal drug use and treatment delays. Metagenomics next-generation sequencing (mNGS) is a swift, efficient, and unbiased method for obtaining microbial nucleic acid sequences. This technology holds promise as a comprehensive diagnostic tool, especially for pathogens undetectable by traditional methods. However, the efficacy of mNGS in the context of congenital heart disease infections remains uncertain. This study aimed to explore the diagnostic value of mNGS for respiratory virus infections post-CHS. Methods: We conducted a retrospective analysis of patients who developed respiratory tract infections post-CHS and were admitted to our cardiac center between July 2021 and December 2022. The patients were categorized into the following two groups based on the diagnostic method used: (I) the mNGS group (comprising 62 patients); and (II) the conventional microbiological test (CMT) group (comprising 70 patients). Bronchoalveolar lavage fluid (BALF) samples from these patients were tested to identify pathogens. Results: The mNGS group had significantly higher detection rates for both viral infections and mixed viral infections than the CMT group (56.45% vs. 17.14%, P<0.001, and 80.00% vs. 16.67%, P<0.001, respectively). In the mNGS group, 19.35% of the patients received antiviral therapy, and 61.29% received an anti-infective regimen adjustment. Conversely, in the CMT group, only 4.29% received antiviral therapy, and 28.57% received an anti-infective regimen adjustment. A higher percentage of patients showed improved respiratory symptoms in the mNGS group than the CMT group (74.19% vs. 44.29%, P=0.001). Additionally, the mNGS group had a shorter duration of mechanical ventilation and a reduced length of stay in the cardiac intensive care unit than the CMT group (P=0.012). Conclusions: Using mNGS for BALF enhances the detection of respiratory viral infections and coexisting viral infections post-CHS. This facilitates more precise treatment strategies and could potentially lead to improved patient outcomes.

Genome-wide analysis of ATP-binding cassette (ABC) transporter in Penaeus vannamei and identification of two ABC genes involved in immune defense against Vibrio parahaemolyticus by affecting NF-κB signaling pathway.

The ATP-binding cassette (ABC) transporters have crucial roles in various biological processes such as growth, development and immune defense in eukaryotes. However, the roles of ABC transporters in the immune system of crustaceans remain elusive. In this study, 38 ABC genes were systematically identified and characterized in Penaeus vannamei. Bioinformation analysis revealed that PvABC genes were categorized into ABC A-H eight subfamilies with 17 full-transporters, 11 half transporters and 10 soluble proteins, and multiple immunity-related cis-elements were found in gene promoter regions. Expression analysis showed that most PvABC genes were widely and highly expressed in immune-related tissues and responded to the stimulation of Vibrio parahaemolyticus. To investigate whether PvABC genes mediated innate immunity, PvABCC5, PvABCF1 and PvABCB4 were selected for dsRNA interference experiment. Knockdown of PvABCF1 and PvABCC5 not PvABCB4 increased the cumulative mortality of P. vannamei and bacterial loads in hepatopancreas after infection with V. parahaemolyticus. Further analysis showed that the PvABCF1 and PvABCC5 knockdown decreased expression levels of NF-κB pathway genes and antimicrobial peptides (AMPs). Collectively, these findings indicated that PvABCF1 and PvABCC5 might restrict V. parahaemolyticus challenge by positively regulating NF-κB pathway and then promoting the expression of AMPs, which would contribute to overall understand the function of ABC genes in innate immunity of invertebrates.

Metagenomic Next-generation Sequencing for Pathogen Identification in Bronchoalveolar Lavage Fluid From Neonates Receiving Extracorporeal Membrane Oxygenation.

BACKGROUND: Neonates on extracorporeal membrane oxygenation (ECMO) are at high risk of infection. Rapid and accurate identification of pathogens is essential to improve the prognosis of children on ECMO. Metagenome next-generation sequencing (mNGS) has been used in recent years to detect pathogenic bacteria, but evidence for its use in neonates on ECMO is lacking. METHODS: This retrospective study was conducted using an electronic medical record system. We analyzed the results of mNGS and conventional microbiological tests (CMTs) in bronchoalveolar lavage fluid of neonates receiving ECMO support with pulmonary infections in our hospital from July 2021 to January 2023. RESULTS: We screened 18 ECMO-supported neonates with pneumonia for inclusion in the study. The median age of the included children was 2 (1-4) days, the median gestational age was 38.3 (33-40 +4 ) weeks, and the median weight was 3.3 (2.2-4.8) kg. The detection rate of mNGS was 77.8% (14/18), higher than the 44.4% (8/18) of CMT ( P = 0.04). A total of 20 pathogens were detected in mNGS, with the top 3 most common pathogens being Klebsiella pneumoniae , Acinetobacter baumannii and Escherichia coli . Mixed infections were found in 14 cases (77.8%), including 13 cases (72.2%) with mixed infections detected by mNGS and 7 cases (27.8%) with mixed infections detected by CMT. A total of 9 children underwent treatment changes based on mNGS results and all of them experienced relief of symptoms. CONCLUSION: Compared with CMT, mNGS can detect pathogens earlier and more sensitively, and may play an important role in ECMO-supported neonatal pneumonia pathogen detection and optimization of antibiotic therapy.

The research progression of direct NLRP3 inhibitors to treat inflammatory disorders.

The NLRP3 inflammasome represents a cytoplasmic multiprotein complex with the capability to recognize a wide range of pathogen-derived, environmental, and endogenous stress-related factors. Dysregulated activation of the NLRP3 inflammasome has been implicated in the development of various inflammasome-associated disorders, highlighting its significance as a pivotal target for the treatment of inflammatory diseases. Nonetheless, despite its clinical importance, there is currently a lack of specific drugs available for directly targeting the NLRP3 inflammasome. Several strategies have been explored to target different facets of the NLRP3 inflammasome, with interventions aimed at directly inhibiting NLRP3 demonstrating the most promising efficacy and safety profiles. In this review, we provide a summary of direct inhibitors targeting NLRP3, elucidating their inhibitory mechanisms, clinical trial phases, and potential applications. Through this discussion, we aim to shed light on the implications of NLRP3 inhibition for the treatment of inflammatory diseases.

Prospective cohort study on tuberculosis incidence and risk factors in the elderly population of eastern China.

Background: Tuberculosis continues to be a significant public health concern in China, particularly among the elderly population. This study aimed to assess the risk factors of tuberculosis among elderly individuals in China through a cohort study, focusing on this high-risk population. Methods: The population-based census was strategically designed to cover diverse regions and demographics across the city. The survey captured demographic and lifestyle information, as well as a clinical examination. Participants were prospectively followed up over a specified duration to monitor the incidence of tuberculosis cases. Results: After a follow-up period of more than 7 years, 246 individuals developed tuberculosis, resulting in an incidence rate of 92.21 per 100,000 person-years (95 % CI 81.2-104.3). In multivariate analysis, the following factors were found to have significant associations with active tuberculosis. Increasing age correlated with a higher risk of active tuberculosis (AHR = 1.03 per 1-year increase in age, 95%CI: 1.01, 1.04, P < 0.001). Males continued to have a higher risk compared to females (HR = 2.73, 95%CI: 2.08, 3.58, P < 0.001). Individuals with a normal Body Mass Index (BMI) faced nearly three times higher risk compared to their obese counterparts (HR = 2.87, 95 % CI: 1.51, 5.46, P = 0.001). Conversely, those with an underweight BMI had a ten-fold higher risk compared to the obese group (HR = 9.89, 95 % CI: 4.92, 19.85, P < 0.001). Elderly individuals who quit smoking had a 1.35-fold increased risk compared to non-smokers (HR = 1.35, 95%CI: 1.12, 1.64, P < 0.001). Conclusions: Tuberculosis incidence among the elderly population in China remained alarmingly high. This finding emphasizes the urgent need for implementing proactive case detection measures specifically tailored to address the specific needs of this vulnerable demographic, particularly in individuals who are male, have a history of former or current smoking, and have a low BMI. Moreover, we must not underestimate the influence of former smoking on tuberculosis risk.