Ultra-high-speed four-dimensional hyperspectral imaging.

We propose, to the best of our knowledge, a novel deep learning-enabled four-dimensional spectral imaging system composed of a reflective coded aperture snapshot spectral imaging system and a panchromatic camera. The system simultaneously captures a compressively coded hyperspectral measurement and a panchromatic measurement. The hyperspectral data cube is recovered by the U-net-3D network. The depth information of the scene is then acquired by estimating a disparity map between the hyperspectral data cube and the panchromatic measurement through stereo matching. This disparity map is used to align the hyperspectral data cube and the panchromatic measurement. A designed fusion network is used to improve the spatial reconstruction of the hyperspectral data cube by fusing aligned panchromatic measurements. The hardware prototype of the proposed system demonstrates high-speed four-dimensional spectral imaging that allows for simultaneously acquiring depth and spectral images with an 8 nm spectral resolution between 450 and 700 nm, 2.5 mm depth accuracy, and a 1.83 s reconstruction time.

Comorbidities among adult patients with psoriasis in Tianjin: a cross-sectional analysis of the Health Database study.

OBJECTIVES: This study aims to examine the prevalence of comorbidities in adult patients with psoriasis and compare them with those in control subjects without psoriasis in Tianjin, China. DESIGN: The study is a cross-sectionalanalysis. PARTICIPANTS: The participants were established by identifying all patients (age ≥18 years) who visited hospitals and clinics in Tianjin between 1 January 2016 and 31 October 2019. SETTING: The study group consisted of 20 678 adult patients with psoriasis, and a comparison group was created after 1:1 propensity score matching. Logistic regression analyses were conducted to examine the risk of 22 comorbidities for these two groups. RESULTS: Patients with psoriasis had a significantly higher prevalence of 11 comorbidities and a lower prevalence of 2 comorbidities within 12 months of follow-up. Our results also showed that the proportion of psoriatic arthritis might account for approximately 2% of all patients with psoriasis. This psoriatic arthritis group had a higher average age and CCI (Charlson Comorbidity Index) index score (2.27 >1.62, p <0.001) than the non-arthritis group. CONCLUSIONS: This study showed that psoriasis in Tianjin is associated with various comorbidities. It also emphasises the importance of clinical treatment in improving therapeutic effects and reducing the burden of psoriasis in China.

Opioid-Sparing Anesthesia Versus Opioid-Free Anesthesia for the Prevention of Postoperative Nausea and Vomiting after Laparoscopic Bariatric Surgery: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Patients who undergo laparoscopic bariatric surgery (LBS) are susceptible to postoperative nausea and vomiting (PONV). Opioid-free anesthesia (OFA) or opioid-sparing anesthesia (OSA) protocols have been proposed as solutions; however, differences between the 2 alternative opioid protocols for anesthesia maintenance in obese patients remain uncertain. A network meta-analysis was conducted to compare the impacts of OFA and OSA on PONV. METHODS: Systematic searches were conducted using Embase, PubMed, MEDLINE, and Cochrane Library databases to identify randomized controlled trials (RCTs) comparing OFA and OSA strategies. After screening according to the inclusion and exclusion criteria, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the credibility of the evidence. The main concern of this review was the difference between OFA and OSA in reducing PONV. The primary outcome was any PONV occurrence within 24 hours. Secondary outcomes included postoperative pain intensity, opioid consumption, opioid-related adverse events, and length of hospital stay. RESULTS: Fifteen RCTs involving 1310 patients were identified for a network meta-analysis from 1776 articles that compared OFA, OSA, and traditional opioid-based anesthesia (OBA) strategies in LBS. Twelve RCTs (80%) with 922 participants (70%) were eligible for the occurrence of PONV. These included 199 (22%) patients who received OFA and 476 (52%) and 247 (27%) patients who received OSA and OBA, respectively. OFA was more effective at reducing PONV (relative risks [RR], 0.6, 95% confidence interval [CI], 0.5-0.9, moderate-quality evidence) compared to OSA. No differences were observed in postoperative pain control or opioid consumption between the OFA and OSA strategies (very low-to high-quality evidence). Notably, OFA is associated with a higher risk of bradycardia than OSA (RR, 2.6, 95% CI, 1.2-5.9, moderate-quality evidence). CONCLUSIONS: OFA is more effective than OSA in reducing the occurrence of PONV during the early postoperative period of LBS, although it may associate with an increased risk of bradycardia. Patients who received either opioid-alternative strategy demonstrated similar effects in reducing postoperative opioid consumption and alleviating pain intensity.

Pulmonary succinate receptor 1 elevation in high-fat diet mice exacerbates lipopolysaccharides-induced acute lung injury via sensing succinate.

BACKGROUND: Individuals with obesity have higher level of circulating succinate, which acts as a signaling factor that initiates inflammation. It is obscure whether succinate and succinate receptor 1 (SUCNR1) are involved in the process of obesity aggravating acute lung injury (ALI). METHODS: The lung tissue and blood samples from patients with obesity who underwent lung wedgectomy or segmental resection were collected. Six-week-old male C57BL/6J mice were fed a high-fat diet for 12 weeks to induce obesity and lipopolysaccharides (LPS) were injected intratracheally (100 µg, 1 mg/ml) for 24 h to establish an ALI model. The pulmonary SUCNR1 expression and succinate level were measured. Exogenous succinate was supplemented to assess whether succinate exacerbated the LPS-induced lung injury. We next examined the cellular localization of pulmonary SUCNR1. Furthermore, the role of the succinate-SUCNR1 pathway in LPS-induced inflammatory responses in MH-s macrophages and obese mice was investigated. RESULT: The pulmonary SUCNR1 expression and serum succinate level were significantly increased in patients with obesity and in HFD mice. Exogenous succinate supplementation significantly increased the severity of ALI and inflammatory response. SUCNR1 was mainly expressed on lung macrophages. In LPS-stimulated MH-s cells, knockdown of SUCNR1 expression significantly inhibited pro-inflammatory cytokines' expression, the increase of hypoxia-inducible factor-1α (HIF-1α) expression, inhibitory κB-α (IκB-α) phosphorylation, p65 phosphorylation and p65 translocation to nucleus. In obese mice, SUCNR1 inhibition significantly alleviated LPS-induced lung injury and decreased the HIF-1α expression and IκB-α phosphorylation. CONCLUSION: The high expression of pulmonary SUCNR1 and serum succinate accumulation at least partly participate in the process of obesity aggravating LPS-induced lung injury.

Obesity-induced downregulation of miR-192 exacerbates lipopolysaccharide-induced acute lung injury by promoting macrophage activation.

BACKGROUND: Macrophage activation may play a crucial role in the increased susceptibility of obese individuals to acute lung injury (ALI). Dysregulation of miRNA, which is involved in various inflammatory diseases, is often observed in obesity. This study aimed to investigate the role of miR-192 in lipopolysaccharide (LPS)-induced ALI in obese mice and its mechanism of dysregulation in obesity. METHODS: Human lung tissues were obtained from obese patients (BMI ≥ 30.0 kg/m2) and control patients (BMI 18.5-24.9 kg/m2). An obese mouse model was established by feeding a high-fat diet (HFD), followed by intratracheal instillation of LPS to induce ALI. Pulmonary macrophages of obese mice were depleted through intratracheal instillation of clodronate liposomes. The expression of miR-192 was examined in lung tissues, primary alveolar macrophages (AMs), and the mouse alveolar macrophage cell line (MH-S) using RT-qPCR. m6A quantification and RIP assays helped determine the cause of miR-192 dysregulation. miR-192 agomir and antagomir were used to investigate its function in mice and MH-S cells. Bioinformatics and dual-luciferase reporter gene assays were used to explore the downstream targets of miR-192. RESULTS: In obese mice, depletion of macrophages significantly alleviated lung tissue inflammation and injury, regardless of LPS challenge. miR-192 expression in lung tissues and alveolar macrophages was diminished during obesity and further decreased with LPS stimulation. Obesity-induced overexpression of FTO decreased the m6A modification of pri-miR-192, inhibiting the generation of miR-192. In vitro, inhibition of miR-192 enhanced LPS-induced polarization of M1 macrophages and activation of the AKT/ NF-κB inflammatory pathway, while overexpression of miR-192 suppressed these reactions. BIG1 was confirmed as a target gene of miR-192, and its overexpression offset the protective effects of miR-192. In vivo, when miR-192 was overexpressed in obese mice, the activation of pulmonary macrophages and the extent of lung injury were significantly improved upon LPS challenge. CONCLUSIONS: Our study indicates that obesity-induced downregulation of miR-192 expression exacerbates LPS-induced ALI by promoting macrophage activation. Targeting macrophages and miR-192 may provide new therapeutic avenues for obesity-associated ALI.

Microarray analysis identifies lncFirre as a potential regulator of obesity-related acute lung injury.

AIMS: The inflammatory response in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is heightened in obesity. The aim of this study was to investigate whether lncRNAs are involved in the effects of obesity on acute lung injury and to find possible effector lncRNAs. MAIN METHODS: Microarray analysis was used to assess the transcriptional profiles of lncRNAs and mRNAs in lung tissues from normal (CON), high-fat diet induced obese (DIO), and obese ALI mice (DIO-ALI). GO and KEGG analyses were employed to explore the biological functions of differentially expressed genes. A lncRNA-mRNA co-expression network was constructed to identify specific lncRNA. Lung tissues and peripheral blood samples from patients with obesity and healthy lean donors were utilized to confirm the expression characteristics of lncFirre through qRT-PCR. lncFirre was knocked down in MH-S macrophages to explore its function. ELISA and Griess reagent kit were used to detect PGE2 and NO. Flow cytometry was used to detect macrophages polarization. KEY FINDINGS: There were 475 lncRNAs and 404 mRNAs differentially expressed between DIO and CON, while 1348 lncRNAs and 1349 mRNAs between DIO-ALI and DIO. Obesity increased lncFirre expression in both mice and patients, and PA elevated lncFirre in MH-S. PA exacerbated the inflammation and proinflammatory polarization of MH-S induced by LPS. LncFirre knockdown inhibited the secretion of PGE2 and NO, M1 differentiation while promoted the M2 differentiation in PA and LPS co-challenged MH-S. SIGNIFICANCE: Interfering with lncFirre effectively inhibit inflammation in MH-S, lncFirre can serve as a promising target for treating obesity-related ALI.

Gut dysbiosis contributes to chlamydial induction of hydrosalpinx in the upper genital tract.

Chlamydia trachomatis is one of the most common sexually infections that cause infertility, and its genital infection induces tubal adhesion and hydrosalpinx. Intravaginal Chlamydia muridarum infection in mice can induce hydrosalpinx in the upper genital tract and it has been used for studying C. trachomatis pathogenicity. DBA2/J strain mice were known to be resistant to the chlamydial induction of hydrosalpinx. In this study, we took advantage of this feature of DBA2/J mice to evaluate the role of antibiotic induced dysbiosis in chlamydial pathogenicity. Antibiotics (vancomycin and gentamicin) were orally administrated to induce dysbiosis in the gut of DBA2/J mice. The mice with or without antibiotic treatment were evaluated for gut and genital dysbiosis and then intravaginally challenged by C. muridarum. Chlamydial burden was tested and genital pathologies were evaluated. We found that oral antibiotics significantly enhanced chlamydial induction of genital hydrosalpinx. And the antibiotic treatment induced severe dysbiosis in the GI tract, including significantly reduced fecal DNA and increased ratios of firmicutes over bacteroidetes. The oral antibiotic did not alter chlamydial infection or microbiota in the mouse genital tracts. Our study showed that the oral antibiotics-enhanced hydrosalpinx correlated with dysbiosis in gut, providing the evidence for associating gut microbiome with chlamydial genital pathogenicity.

Promising application of a new ulnar nerve compound muscle action potential measurement montage in amyotrophic lateral sclerosis: a prospective cross-sectional study.

Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional "belly-tendon" montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles. A new method of ulnar nerve compound muscle action potential measurement was developed in 2020, which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist. This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential. In this prospective cross-sectional study, we included 64 patients with amyotrophic lateral sclerosis and 64 age- and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital. The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage. In the controls, no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings. In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy, the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2 (P < 0.01). Using the new method, damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method, in particular for patients in early stage amyotrophic lateral sclerosis. In addition, the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position, and that this method is more suitable for monitoring disease progression than the traditional montage. This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.

Activation of PPARγ Protects Obese Mice from Acute Lung Injury by Inhibiting Endoplasmic Reticulum Stress and Promoting Mitochondrial Biogenesis.

Objective: Obesity-induced endoplasmic reticulum (ER) stress plays a role in increased susceptibility to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The activation of peroxisome proliferator-activated receptor-γ (PPARγ) is associated with lung protection and is effective in ameliorating ER stress and mitochondrial dysfunction. The aim of this study was to investigate the expression of PPARγ in the lung tissues of obese mice and explore whether the PPARγ-dependent pathway could mediate decreased ALI/ARDS by regulating ER stress and mitochondrial biogenesis. Methods: We determined PPARγ expression in the lung tissues of normal and obese mice. ALI models of alveolar epithelial cells and of obese mice were used and treated with either PPARγ activator rosiglitazone (RSG) or PPARγ inhibitor GW9662. Lung tissue and cell samples were collected to assess lung inflammation and apoptosis, and ER stress and mitochondrial biogenesis were detected. Results: PPARγ expression was significantly decreased in the lung tissue of obese mice compared with that in normal mice. Both in vivo and in vitro studies have shown that activation of PPARγ leads to reduced expression of the ER stress marker proteins 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and Caspase12. Conversely, expression of the mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) increased. Furthermore, activation of PPARγ is associated with decreased levels of lung inflammation and epithelial apoptosis and increased expression of adiponectin (APN) and mitofusin2 (MFN2). GW9662 bound to PPARγ and blocked its transcriptional activity and then diminished the protective effect of PPARγ on lung tissues. Conclusions: PPARγ activation exerts anti-inflammation effects in alveolar epithelia by alleviating ER stress and promoting mitochondrial biogenesis. Therefore, lower levels of PPARγ in the lung tissues of obese mice may lead to an increased susceptibility to ALI.

The Impact of Goal-Directed Fluid Therapy on Postoperative Nausea and Vomiting in High-Risk Patients Undergoing Laparoscopic Sleeve Gastrectomy.

PURPOSE: Patients with laparoscopic sleeve gastrectomy (LSG) are at high risk of postoperative nausea and vomiting (PONV). Goal-directed fluid therapy (GDFT) has been proven effective in improving postoperative gastrointestinal function in patients with obesity, but its effect on prevention of PONV remains controversial. This study aimed to investigate the impact of GDFT on PONV in high-risk patients with LSG. METHODS: In a randomized, single-blinded, two-arm trial, patients with an Apfel score ≥ 3 and scheduled for LSG were included. Patients in the GDFT group received stroke volume-guided fluid therapy. Patients in the control group received conventional fluid therapy. The primary outcome was the incidence of PONV within 48 h after LSG. The second outcome included intensity of PONV, use of rescue therapy, recovery of gastrointestinal function, and postoperative length of stay (LOS). RESULTS: A total of 137 patients were analyzed. The incidence of PONV in the GDFT group was lower than that in the control group (47.1% vs. 71.6%; odds ratio [95%CI], 0.35 [0.17-0.72]; P = 0.004). Fewer patients in the GDFT group received rescue therapy (30% vs. 58.2%; P = 0.001). Patients following GDFT protocol had a faster return of flatus (27.5 (19, 31) vs. 31 (20, 48) hours, P = 0.037) and shorter postoperative LOS (6.1 ± 1.0 vs. 6.6 ± 1.1 days; P = 0.007). CONCLUSION: GDFT is conducive to deceasing PONV occurrence, restoring intestinal function, and shortening postoperative LOS in high-risk patients undergoing LSG.

Ultra-early amplitude decrement after repetitive nerve stimulation supports early neuromuscular junction injury in amyotrophic lateral sclerosis: a prospective cross-sectional study.

The dying-back hypothesis holds that the damage to neuromuscular junctions and distal axons in amyotrophic lateral sclerosis occurs at the earliest stage of the disease. Previous basic studies have confirmed early damage to neuromuscular junctions, but it is difficult to obtain such evidence directly in clinical practice. In this prospective cross-sectional study, we recruited 22 patients with early amyotrophic lateral sclerosis with disease duration < 12 months and with clinical symptoms limited to the upper limbs. We also recruited 32 healthy controls. Repetitive nerve stimulation was performed, and patients were followed for 12 months. We found a significant change in the response to repetitive nerve stimulation in amyotrophic lateral sclerosis patients without spontaneous electromyographic activity. Patients that were prone to denervation had an increased decrement response of target muscles after repetitive nerve stimulation. These results suggest that changes in response to repetitive nerve stimulation may occur before denervation in amyotrophic lateral sclerosis patients. The damage to lower motor neurons is more obvious in patients with a higher percentage of repetitive never stimulation-related amplitude decrements. This study was approved by the Institutional Ethics Committee of Peking University Third Hospital (approval No. M2017198) on August 24, 2017.

Trends in the clinical features of amyotrophic lateral sclerosis: A 14-year Chinese cohort study.

BACKGROUND AND PURPOSE: The aim was to determine the transitional patterns in the clinical characteristics, treatments and comorbidities in amyotrophic lateral sclerosis (ALS) patients over the past 14 years using data from a large clinical cohort in mainland China. METHODS: Sporadic ALS patients who visited the Peking University Third Hospital from January 2005 to December 2018 were included in this study. The 14 years were divided into three periods, and changes in the baseline characteristics of the participants were analyzed at 5-year intervals. RESULTS: In total, 3410 patients with sporadic ALS were recruited: 2181 were men and 1229 were women. The proportion of patients with bulbar-onset ALS increased from 13.0% in 2005-2009 to 19.5% in 2015-2018 (p < 0.001). The mean (standard deviation) age at onset increased from 49.5 (11.4) years in 2005-2009 to 53.0 (11.0) years in 2015-2018 (p < 0.001). ALS patients with diabetes or hypertension showed a delay in ALS onset, and the delay was even more apparent when the patients had both comorbidities. The proportion of riluzole users in 2015-2018 was approximately 2.5-fold of that in 2005-2009 (p < 0.001). CONCLUSIONS: In the context of a lack of clinical data on ALS in mainland China, this study evaluated a large cohort of patients diagnosed over a 14-year period. The age at onset and percentage of patients who used riluzole both increased over the study period. Additionally, it was found that patients with comorbidities such as diabetes and hypertension had a delayed age of ALS onset.

Transcutaneous Electrical Acupoint Stimulation Combined with Dexamethasone and Tropisetron Prevents Postoperative Nausea and Vomiting in Female Patients Undergoing Laparoscopic Sleeve Gastrectomy: a Prospective, Randomized Controlled Trial.

BACKGROUND: Despite the administration of prophylactic antiemetics, some patients who undergo laparoscopic sleeve gastrectomy (LSG) remain at high risk for postoperative nausea and vomiting (PONV). Although many trials have been conducted, the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on the prevention of PONV remains unknown. METHODS: Sixty-two female patients undergoing elective LSG were randomly assigned to the TEAS combined with dexamethasone and tropisetron (TEAS group, n = 31) or dexamethasone and tropisetron (control group, n = 31) groups. The incidence and severity of PONV, as well as the need for rescue antiemetics, were collected within 48 h after surgery. RESULTS: The patients in both groups had similar clinical characteristics and underwent the same surgical procedure. In the TEAS group, 13 patients (41.9%) had PONV within 48 h after LSG compared to 24 patients (77.4%) in the control group (P = 0.004, relative risk: 0.39 [0.19, 0.80]). The severity of PONV differed significantly between groups, with five patients (16.1%) in the TEAS group and 15 patients (48%) in the control group experiencing clinically important PONV (P = 0.007, relative risk: 0.62 [0.42, 0.90]). Moreover, fewer patients required antiemetic rescue medication in the TEAS group compared with the control group (29.0% vs. 58.1%, P = 0.021). CONCLUSION: Multimodal antiemetic prophylaxis consisting of TEAS and antiemetics was effective in reducing PONV incidence and intensity in high-risk patients undergoing LSG.

The TSN1 Binding Protein RH31 Is a Component of Stress Granules and Participates in Regulation of Salt-Stress Tolerance in Arabidopsis.

Tudor staphylococcal nucleases (TSNs) are evolutionarily conserved RNA binding proteins, which include redundant TSN1 and TSN2 in Arabidopsis. It has been showed TSNs are the components of stress granules (SGs) and regulate plant growth under salt stress. In this study, we find a binding protein of TSN1, RH31, which is a DEAD-box RNA helicase (RH). Subcellular localization studies show that RH31 is mainly located in the nucleus, but under salinity, it translocates to the cytoplasm where it accumulates in cytoplasmic granules. After cycloheximide (CHX) treatment which can block the formation of SGs by interfering with mRNP homeostasis, these cytoplasmic granules disappeared. More importantly, RH31 co-localizes with SGs marker protein RBP47. RH31 deletion results in salt-hypersensitive phenotype, while RH31 overexpression causes more resistant to salt stress. In summary, we demonstrate that RH31, the TSN1 binding protein, is a component of plant SGs and participates in regulation of salt-stress tolerance in Arabidopsis.

The Cryptic Plasmid Improves Chlamydia Fitness in Different Regions of the Gastrointestinal Tract.

The cryptic plasmid is important for chlamydial colonization in the gastrointestinal tract. We used a combination of intragastric, intrajejunal, and intracolon inoculations to reveal the impact of the plasmid on chlamydial colonization in distinct regions of gastrointestinal tract. Following an intragastric inoculation, the plasmid significantly improved chlamydial colonization. At the tissue level, plasmid-positive Chlamydia produced infectious progenies throughout gastrointestinal tract. However, to our surprise, plasmid-deficient Chlamydia failed to produce infectious progenies in small intestine, although infectious progenies were eventually detected in large intestine, indicating a critical role of the plasmid in chlamydial differentiation into infectious particles in small intestine. The noninfectious status may represent persistent infection, since Chlamydia genomes proliferated in the same tissues. Following an intrajejunal inoculation that bypasses the gastric barrier, plasmid-deficient Chlamydia produced infectious progenies in small intestine but was 530-fold less infectious than plasmid-positive Chlamydia, suggesting that (i) the noninfectious status developed after intragastric inoculation might be induced by a combination of gastric and intestinal effectors and (ii) chlamydial colonization in small intestine was highly dependent on plasmid. Finally, following an intracolon inoculation, the dependence of chlamydial colonization on plasmid increased over time. Thus, we have demonstrated that the plasmid may be able to improve chlamydial fitness in different gut regions via different mechanisms, which has laid a foundation to further reveal the specific mechanisms.

The Plasmid-Encoded pGP3 Promotes Chlamydia Evasion of Acidic Barriers in Both Stomach and Vagina.

Although Chlamydia trachomatis is a human genital tract pathogen, chlamydial organisms have frequently been detected in both vaginal and rectal swab samples of animals and humans. The plasmid-encoded pGP3, a genital tract virulence factor, is essential for Chlamydia muridarum to colonize the mouse gastrointestinal tract. However, intracolon inoculation to bypass the gastric barrier rescued the colonization ability of a pGP3-deficient C. muridarum mutant, suggesting that pGP3 is required for C. muridarum to reach but not to colonize the large intestine. The pGP3-deficient mutant was rapidly cleared in the stomach and was 100-fold more susceptible to gastric killing. In mice genetically deficient in gastrin, a key regulator for gastric acid production, or pharmacologically treated with a proton pump inhibitor, the ability of pGP3-deficient C. muridarum to colonize the gastrointestinal tract was rescued. The pGP3-dependent resistance was further recapitulated in vitro with treatments with HCl, pepsin, or sarkosyl. In the genital tract, deficiency in pGP3 significantly reduced C. muridarum survival in the mouse vagina and increased C. muridarum susceptibility to vaginal killing by ∼8 times. The pGP3-deficient C. muridarum was more susceptible to lactic acid killing, and the pGP3 deficiency also significantly increased C. trachomatis susceptibility to lactic acid. The above-described observations together suggest that Chlamydia may have acquired the plasmid-encoded pGP3 to overcome the gastric barrier during its adaptation to the gastrointestinal tract and the pGP3-dependent resistance may enable chlamydial evasion of the female lower genital tract barrier during sexual transmission.

Chlamydial genomic MinD protein does not regulate plasmid-dependent genes like Pgp5.

Chlamydia has a unique intracellular developmental cycle, which has hindered the single protein function study of Chlamydia. Recently developed transformation system of Chlamydia has greatly advanced the chlamydial protein's function research and was used to find that a chlamydial plasmid-encoded Pgp5 protein can down-regulate plasmid-dependent genes. It is assumed, that chlamydial genomic MinD protein has a similar function to Pgp5. However, it is unknown whether MinD protein regulates the same plasmid-dependent genes. We replaced pgp5 gene in the shuttle vector pGFP::CM with minD gene of C. trachomatis (CT0582) or C. muridarum (TC0871). The recombinant plasmid was transformed into plasmid-free organisms-CMUT3 and qRT-PCR was used to detect the transcription level of plasmid-encoded and -dependent genes in these pgp5 deficient organisms. As a readout, GlgA, one of the plasmid-regulated gene products was detected by immunofluorescence assay. After recombination, transformation and plaque purification, the stable transformants CT0582R and TC0871R were generated. In these transformants, the plasmid-dependent genes were up-regulated, alike in the pgp5 premature stop mutant and pgp5 replacement with mCherry mutant. GlgA protein level was also increased in all pgp5 mutants, including CT0582R and TC0871R. Thus, our study showed that genomic MinD protein had different function than Pgp5, which was useful for further understanding the chlamydiae.

[A review of the relationship between gut microbiome and necrotizing enterocolitis in preterm infants].

Necrotizing enterocolitis (NEC) is a common severe gastrointestinal disease in preterm infants. The morbidity and mortality of NEC are negatively correlated with the gestational age and birth weight. In addition to causing a variety of gastrointestinal complications, NEC can also cause neurodevelopmental impairment. Recently, many studies have found that gut microbiome dysbiosis plays an important part in the pathogenesis of NEC. It is helpful to explore the relationship between gut microbiome and NEC for the early diagnosis and severity prediction of NEC. Researchers have paid much attention to the role of probiotics in reducing the morbidity and mortality of NEC in preterm infants. It's controversial as to whether probiotics is effective and safe in clinical application. This article will review the relationship between the development of gut microbiome and NEC in preterm infants, as well as the preventive effect of probiotics on NEC.

Identification of proteins differentially expressed by Chlamydia trachomatis treated with chlamydiaphage capsid protein VP1 during intracellular growth.

Chlamydia trachomatis infection is one of the most prevalent sexually transmitted diseases. Our research pertains to the inhibitory effect and molecular mechanism of the chlamydiaphage capsid protein VP1 on the growth of Chlamydia trachomatis. In this research, the capsid protein VP1 of the guinea-pig conjunctivitis chlamydiaphage phiCPG1 was expressed, purified and identified, and then, it was applied to the cultivation of different serovars of Chlamydia trachomatis and Chlamydia psittaci. The inhibitory effect was observed in each serovar of Chlamydia trachomatis (D, E, F, G, H, I, K, and L2) and Chlamydia psittaci inoculated with VP1 protein. The inhibition affection of VP1 on the growth of Chlamydia trachomatis was caused by the changes of expressions of some related proteins including 36 proteins up-regulated and 81 proteins down-regulated in the development cycle of Ct through the label-free test, and the transcription levels of these proteins, including Hc1, pmpD, and MOMP, were confirmed by RT-PCR. It provides information that is essential for understanding the mechanism of chlamydiaphage capsid protein VP1 on chlamydia and a new direction for further clinical treatment of chlamydial infection.