Creg1 Regulates Erythroid Development via TGF-ß/Smad2-Klf1 Axis in Zebrafish.

Understanding the regulation of normal erythroid development will help to develop new potential therapeutic strategies for disorders of the erythroid lineage. Cellular repressor of E1A-stimulated genes 1 (CREG1) is a glycoprotein that has been implicated in the regulation of tissue homeostasis. However, its role in erythropoiesis remains largely undefined. In this study, it is found that CREG1 expression increases progressively during erythroid differentiation. In zebrafish, creg1 mRNA is preferentially expressed within the intermediate cell mass (ICM)/peripheral blood island (PBI) region where primitive erythropoiesis occurs. Loss of creg1 leads to anemia caused by defective erythroid differentiation and excessive apoptosis of erythroid progenitors. Mechanistically, creg1 deficiency results in reduced activation of TGF-ß/Smad2 signaling pathway. Treatment with an agonist of the Smad2 pathway (IDE2) could significantly restore the defective erythroid development in creg1-/- mutants. Further, Klf1, identified as a key target gene downstream of the TGF-ß/Smad2 signaling pathway, is involved in creg1 deficiency-induced aberrant erythropoiesis. Thus, this study reveals a previously unrecognized role for Creg1 as a critical regulator of erythropoiesis, mediated at least in part by the TGF-ß/Smad2-Klf1 axis. This finding may contribute to the understanding of normal erythropoiesis and the pathogenesis of erythroid disorders.

Neoadjuvant camrelizumab (an anti-PD-1 antibody) plus chemotherapy or apatinib (a VEGFR-2 inhibitor) for initially unresectable stage II-III non-small-cell lung cancer: a multicentre, two-arm, phase 2 exploratory study.

This multicentre, two-arm, phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II-III non-small-cell lung cancer (NSCLC). Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks (arm A) or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily (arm B), for 2-4 cycles, followed by surgery. The primary endpoint was major pathological response (MPR) rate. Thirty patients in arm A and 21 in arm B were enrolled. Surgery rates were 50.0% (15/30) in arm A and 42.9% (9/21) in arm B, with all patients achieving R0 resections. Of these patients, the MPR and pathological complete response rates were both 20.0% (95% CI 4.3-48.1) in arm A and were 55.6% (95% CI 21.2-86.3) and 11.1% (95% CI 0.3-48.2) in arm B, respectively. The corresponding objective response rates were 33.3% (95% CI 11.8-61.6) and 55.6% (95% CI 21.2-86.3). With a median follow-up of 22.4 months (95% CI 19.0-26.0), the median event-free survival was not reached (NR; 95% CI 13.6-NR) in arm A and 16.8 months (95% CI 8.6-NR) in arm B. Grade 3 or above treatment-related adverse events occurred in eight (26.7%) patients in arm A and three (14.3%) in arm B. Biomarker analysis showed baseline TYROBP expression was predictive of treatment response in arm B. Neoadjuvant camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II-III NSCLC.

YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis.

The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

Genomic and functional diversity of the human-derived isolates of Faecalibacterium.

Introduction: Faecalibacterium is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of Faecalibacterium genomes from cultured strains and the distribution of different species in populations may differ among different sources. Methods: We here performed an extensive analysis of pan-genomes, functions, and safety evaluation of 136 Faecalibacterium genomes collected from 10 countries. Results: The genomes are clustered into 11 clusters, with only five of them were characterized and validly nomenclated. Over 80% of the accessory genes and unique genes of Faecalibacterium are found with unknown function, which reflects the importance of expanding the collection of Faecalibacterium strains. All the genomes have the potential to produce acetic acid and butyric acid. Nine clusters of Faecalibacterium are found significantly enriched in the healthy individuals compared with patients with type II diabetes.. Discussion: This study provides a comprehensive view of genomic characteristic and functions and of culturable Faecalibacterium bacterium from human gut, and enables clinical advances in the future.

Opioid-sparing effects of ultrasound-guided erector spinae plane block for video-assisted thoracoscopic surgery: a randomized controlled study.

BACKGROUND: The erector spinae plane block (ESPB) is a new analgesic method used in thoracic surgery. However, few studies have characterized their effects on perioperative opioid consumption. We aimed to evaluate the effects of ESPB on perioperative opioid consumption in patients who underwent video-assisted thoracoscopic surgery (VATS). METHODS: This was a randomized, observer-blinded clinical trial at a single-centre academic hospital. Eighty patients were scheduled for thoracoscopic segmentectomy or lobectomy by VATS for lung cancer. Forty participants were randomly assigned to ESPB or control group. All patients received intravenous patient-controlled postoperative analgesia. Perioperative opioid consumption, visual analogue scale (VAS) scores, and adverse events were recorded. RESULTS: Intraoperative and postoperative opioid consumption and static/dynamic VAS scores were significantly lower in the early hours after VATS in the ESPB group (p < 0.05) than the control group. No significant differences were observed in adverse effects between the two groups. CONCLUSIONS: ESPB reduced intraoperative opioid consumption and early postoperative pain in patients undergoing VATS. Our findings support the view that ESPB is a safe and highly effective option for regional analgesia for VATS. TRIAL REGISTRATION: http://www.chictr.org.cn , ChiCTR1800019335.

A synapse with low power consumption based on MoTe2/SnS2heterostructure.

The use of two-dimensional materials and van der Waals heterostructures holds great potential for improving the performance of memristors Here, we present SnS2/MoTe2heterostructure synaptic transistors. Benefiting from the ultra-low dark current of the heterojunction, the power consumption of the synapse is only 19pJ per switching under 0.1 V bias, comparable to that of biological synapses. The synaptic device based on the SnS2/MoTe2demonstrates various synaptic functionalities, including short-term plasticity, long-term plasticity, and paired-pulse facilitation. In particular, the synaptic weight of the excitatory postsynaptic current can reach 109.8%. In addition, the controllability of the long-term potentiation and long-term depression are discussed. The dynamic range (Gmax/Gmin) and the symmetricity values of the synaptic devices are approximately 16.22 and 6.37, and the non-linearity is 1.79. Our study provides the possibility for the application of 2D material synaptic devices in the field of low-power information storage.

A middle lobe sparing sleeve resection versus bilobectomy for right lower central non-small cell lung cancer: a retrospective propensity score matched cohort study.

OBJECTIVES: The right lower sleeve lobectomy is a rarely performed major lung resection.This study aims to evaluate the safety and effectiveness of this procedure by comparing to right lower bilobectomy in non-small cell lung cancer patients. METHODS: We retrospectively reviewed a prospective database of non-small cell lung cancer patients who underwent right lower sleeve lobectomy (group S) or right lower bilobectomy (group B) from January 2014 to January 2020 in Shanghai Pulmonary Hospital. Propensity score matching method was applied to balance confounders between the two groups, resulting in 41 matched pairs.The analysis was performed to compare perioperative outcomes, long-term survival, and postoperative pulmonary volume between the two groups. RESULTS: No significant differences in the characteristics were observed between the two matched groups.Major postoperative complications developed in 31.7% of the patients in group B and 12.1% of the patients in group S (P = 0.032).Intervention rate for surgical residual cavity in group B is significantly higher than those patients in group S(21.9%vs7.3%,p = 0.037).The postoperative right lateral and overall lung volume in group S were both significantly larger than that in group B (P = 0.026,P = 0.001,respectively). CONCLUSIONS: Compared to bi-lobectomy, a middle lobe sparing sleeve resection obtains a less prevalence of major complications, smaller postoperative residual air space and similar long-term survival for selected central right lower NSCLC patients.

Genomic and functional diversity of cultivated Bifidobacterium from human gut microbiota.

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

Comparison of ultrasound-guided subtransverse process interligamentary plane block with paravertebral block for postoperative analgesia in thoracic surgery: protocol for a randomised non-inferiority trial.

INTRODUCTION: The subtransverse process interligamentary (STIL) plane block is an emerging interfascial plane block that has garnered attention for its potential to provide effective postoperative analgesia for breast and thoracic surgeries. However, a direct comparative assessment between the STIL plane block and the paravertebral block is currently lacking. Consequently, our study aims to assess the analgesic efficacy of the STIL block in comparison to paravertebral block for patients undergoing video-assisted thoracoscopic surgery (VATS). METHODS AND ANALYSIS: This study is a randomised, parallel-controlled, double-blind, non-inferiority trial, with the goal of enrolling 114 participants scheduled for uniportal VATS at Shanghai Pulmonary Hospital. Participants will be randomly assigned in a 1:1 ratio through block randomisation to receive either the STIL plane block (n=57) or the paravertebral block (n=57). The primary outcome of the study is the area under the curve of Numerical Rating Scale(NRS) scores recorded over a 48-hour period following the surgical procedure. Secondary outcomes encompass the evaluation of Quality of Recovery-40, cumulative sufentanil consumption, serum inflammatory factors, rescue medication usage, the incidence of adverse events and the patient satisfaction scores. ETHICS AND DISSEMINATION: This study has received approval from the Medical Ethics Committee of Shanghai Pulmonary Hospital (approval no. L22-329). Written informed consent will be obtained from all participants. The findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2200066909.

Comparison of the DNBSEQ platform and Illumina HiSeq 2000 for bacterial genome assembly.

The Illumina HiSeq platform has been a commonly used option for bacterial genome sequencing. Now the BGI DNA nanoball (DNB) nanoarrays platform may provide an alternative platform for sequencing of bacterial genomes. To explore the impact of sequencing platforms on bacterial genome assembly, quality assessment, sequence alignment, functional annotation, mutation detection, and metagenome mapping, we compared genome assemblies based on sequencing of cultured bacterial species using the HiSeq 2000 and BGISEQ-500 platforms. In addition, simulated reads were used to evaluate the impact of insert size on genome assembly. Genome assemblies based on BGISEQ-500 sequencing exhibited higher completeness and fewer N bases in high GC genomes, whereas HiSeq 2000 assemblies exhibited higher N50. The majority of assembly assessment parameters, sequences of 16S rRNA genes and genomes, numbers of single nucleotide variants (SNV), and mapping to metagenome data did not differ significantly between platforms. More insertions were detected in HiSeq 2000 genome assemblies, whereas more deletions were detected in BGISEQ-500 genome assemblies. Insert size had no significant impact on genome assembly. Taken together, our results suggest that DNBSEQ platforms would be a valid substitute for HiSeq 2000 for bacterial genome sequencing.

Surgery for bronchiectasis-destroyed lung: feasibility of video-assisted thoracoscopic surgery, and surgical outcomes.

OBJECTIVES: To provide the experience of surgical treatment for bronchiectasis-destroyed lung (BDL) and evaluate the feasibility of video-assisted thoracoscopic surgery (VATS). METHODS: BDL patients underwent surgical treatment between January 2013 and June 2018 were included. Logistic regression was performed to assess factors for major complications, and Cox's regression was performed to assess factors affected symptomatic outcome. RESULTS: Totally, 143 patients were treated by VATS (n = 64) and thoracotomy (n = 79). Nine (14.1%) cases scheduled for VATS were converted to thoracotomy for dense adhesions (n = 6) and frozen hilum (n = 3). The VATS group had a median chest tube duration, hospitalization and a time of returning to full activity of 4 days, 5 days and 1.5 months, respectively. Major complications occurred in 28 (19.6%) of all patients, 50.0% after pneumonectomy and 13.4% after lobectomy/extensive lobectomy. Multivariable analysis identified pneumonectomy [odds ratio, 3.64; 95% confidence interval (CI), 1.18-11.21] as a significant predictor for major complications. Overall, 141 (98.6%) patients benefitted from surgery (completely asymptomatic, n = 109; acceptable alleviation, n = 32). Thirty-four patients experienced relapse of the disease, including 13 with productive cough, 11 with haemoptysis and 10 with recurrent infections. Pseudomonas aeruginosa infection [hazard ratio (HR), 3.07; 95% CI, 1.38-6.83] and extent of remanent bronchiectatic areas (HR, 1.03; 95% CI, 1.00-1.05) were independent risk factors for shorter relapse free interval. CONCLUSIONS: VATS for BDL is feasible in well-selected patients. Pneumonectomy increased the risk of postoperative major complications. Removing all BDL lesions contributed to satisfactory prognosis.

Impact of molecular structure of starch on the glutinous taste quality of cooked chestnut kernels.

Chestnuts are a starchy food with a characteristic glutinous taste that is often used to assess their quality. In this study, our findings indicated that chestnuts with higher glutinous taste quality had lower amylose content and microcrystalline structures, as well as higher subcrystalline structures and relative crystallinity in both the raw and steamed starches. In the leached starch, chestnuts with higher glutinous taste quality had lower amylopectin B1 chains and microcrystalline structure, but higher amylopectin B2 chains, subcrystalline structure and relative crystallinity. These results suggest that amylose content, relative crystallinity, and amylopectin chain length distribution are important factors determining the glutinous taste quality of chestnuts. To further enhance our understanding of these factors, an sensory evaluation model was developed based on textural profile analysis parameters. This study provides valuable insights into the relationship between molecular structure of starch and the glutinous taste quality of starchy foods.

Comparison of erector spinae plane block and serratus anterior plane block for postoperative analgesia in uniportal thoracoscopic lobectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain remains a significant concern following uniportal thoracoscopic surgery. The analgesic efficacy of erector spinae plane block (ESPB) and serratus anterior plane block (SAPB) in terms of postoperative opioid consumption in uniportal thoracoscopic surgery still needs further studies. METHODS: A randomized controlled trial was conducted, enrolling 150 patients who underwent uniportal thoracoscopic lobectomy. The patients were randomly allocated to three groups in a 1:1:1 ratio: the ESPB group (administered 20 ml of 0.5% ropivacaine), the SAPB group (administered 20 ml of 0.5% ropivacaine), and the standard care (control) group. The primary endpoint was the consumption of sufentanil during the first 24 h following surgery. Secondary endpoints assessed the area under the curve (AUC) of pain numerical rating scale (NRS) scores, occurrence of moderate to severe pain, time to initial sufentanil request, and postoperative adverse events. RESULTS: No significant difference was observed in the consumption of sufentanil during the first 24 h following surgery between the ESPB and SAPB groups (adjusted difference, 1.53 [95% CI, -5.15 to 2.08]). However, in comparison to the control group, both intervention groups demonstrated a significant decrease in sufentanil consumption, with adjusted differences of -9.97 [95% CI, -13.10 to -6.84] for the ESPB group and -12.55 [95% CI, -15.63 to -9.47] for the SAPB group. There were no significant differences in AUC of NRS scores during rest and movement between the ESPB and SAPB groups, with adjusted differences of -7.10 [95% CI, 1.33 to -15.55] for the rest condition and 5.61 [95% CI, -13.23 to 2.01] for the movement condition. At 6 h postoperatively, there were fewer patients with moderate to severe pain in the ESPB group compared with those in the SAPB group (adjusted difference, -1.37% [95% CI, -2.29% to -0.45%]. The time to first sufentanil request significantly differed among the three groups (ESPB vs Control P < 0.01, SAPB vs Control P < 0.01, ESPB vs SAPB P = 0.015). CONCLUSIONS: In patients undergoing uniportal thoracoscopic lobectomy, although the differences between the two groups are not statistically significant, both the ESPB and SAPB demonstrate effective reduction in postoperative opioid consumption and the need for rescue analgesics compared to the control group. Moreover, the ESPB group experienced a significantly lower incidence of moderate to severe pain at 6 h postoperatively compared to the SAPB group. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration No: ChiCTR1900021695, Date of registration: March 5th, 2019).

First Report of Fusarium ipomoeae Causing leaf rot on Hosta plantaginea in China.

Hosta plantaginea is an important horticultural plant with ornamental value and is widely cultivated in China. Since April 2022, leaf rot has been observed in the H. plantaginea plants in Wanzhou District, Chongqing City, China (31º14'58"N, 108º53'25"E), the initial symptom is a yellow and brown lesion on the edge of the leaf, in the late stage, brown blighted tissue caused leaves to curl and abscise. Ten typical diseased leaves were collected, the margins of infected tissues were cut into small pieces (5×5 mm) and were sterilized in 75% Ethanol for 30 s, 3% sodium hypochlorite for 3 min, rinsed three times with sterile water, then dried on sterile filter paper and placed to potato dextrose agar (PDA) medium at 25℃for 4 days. Thirteen isolates with morphological characteristics similar to those of Fusarium spp. (Nelson et al. 1983) were recovered. These isolates had white, pink and yellowish mycelia, two isolates produced irregular colonies, and remaining isolates showed round. Two of each type were selected for intensive study (yz2, yz11, yz9 and yz17). The colony of yz2 reached 62 mm in diameter on PDA medium after seven days, macroconidia were elongated sickle-shaped, 3-5 septa, and 12.92 to 21.49 × 3.42 to 5.90 µm in size, microconidia were oval and measured 5.69 to 12.95 × 3.41 to 9.80 µm in size, conidiophores were whorled and branched, yz9 attained 74 mm in diameter after nine days, macroconidia were curved sickle-shaped and apex cell acuminate, 26.9 to 57.2 × 2.4 to 7.1 µm, 3-5 septa. The microconidia were fusiform, 17.8 to 28.8 × 11.2 to 14.5 µm. Conidiophores variable in length. Genomic DNA was extracted from 7-day-old aerial mycelia of four strains (yz2, yz9, yz11 and yz17). The internal transcribed spacer (ITS) region (White et al. 1990), translation elongation factor (EF-1α) (Cao et al. 2014) and partial RNA polymerase second largest subunit (RPB2) (Wang et al. 2019) gene regions were amplified and multilocus phylogenetic analysis was conducted, their sequences were deposited in NCBI Genbank with the following accession numbers: the strains of yz2 and yz11 with OQ829372 and OR236201 for ITS, OQ848594 and OR282462 for EF-1α, OR492296 and OR492297 for RPB2; yz9 and yz17 with OQ829383 and OR236222 for ITS, OQ848595 and OR282463 for EF-1α, OR492295 and OR492298 for RPB2. The ModelFinder was used to select the best-fit model in PhyloSuite v1.2.2, the Bayesian Inference method (BI) analysis was used to estimate the system relationship, yz9 and yz17 were identified as Fusarium ipomoeae, yz2 and yz11 were identified as Fusarium tricinctum. To verify Koch's postulates, 8 healthy plants of H. plantaginea (two-year-old) grown were rinsed with sterile water, after 5 leaves per plant were stabbed with a sterilized needle, 4 plants were inoculated with conidial suspension (1×106 conidia mL-1), other plants injected with sterile water as control, then placed in a greenhouse maintained with 95% relative humidity at 25 ± 1°C. The symptoms on the leaves were similar to field after inoculation for 7 days, whereas all control leaves remained healthy. The same pathogen was re-isolated and re-identified based on multilocus phylogenetic analysis, fulfilling Koch's postulates. To our knowledge, this is the first report of F. ipomoeae causing leaf rot on H. plantaginea in China. In addition, F. ipomoeae was reported to cause leaf spot in Peanut (Xu et al. 2021), and F. tricinctum can cause fruit rot on navel orange in China (Yang et al. 2023). H. plantaginea as a horticultural plant is popular with some people, but it has long been threatened by Fusarium.spp. The finding can provide a theoretical basis for control leaf rot on H. plantaginea.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.

Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.

Use of an autologous dermal flap and rib cartilage graft in the repair of a large tracheoesophageal fistula with tracheal stenosis.

Management of large tracheoesophageal fistulas complicated by tracheal stenosis remains challenging as it requires an ideal replacement for the membranous defect as well as a permanent buttress to reconstruct the stenotic segment. We present the successful use of an autologous free dermal flap reinforced with a pedicled pectoralis major muscle to repair the tracheal membranous wall and a rib cartilage graft to enlarge the tracheal lumen.

A catalog of bacterial reference genomes from cultivated human oral bacteria.

The oral cavity harbors highly diverse communities of microorganisms. However, the number of isolated species and high-quality genomes is limited. Here we present a Cultivated Oral Bacteria Genome Reference (COGR), comprising 1089 high-quality genomes based on large-scale aerobic and anaerobic cultivation of human oral bacteria isolated from dental plaques, tongue, and saliva. COGR covers five phyla and contains 195 species-level clusters of which 95 include 315 genomes representing species with no taxonomic annotation. The oral microbiota differs markedly between individuals, with 111 clusters being person-specific. Genes encoding CAZymes are abundant in the genomes of COGR. Members of the Streptococcus genus make up the largest proportion of COGR and many of these harbor entire pathways for quorum sensing important for biofilm formation. Several clusters containing unknown bacteria are enriched in individuals with rheumatoid arthritis, emphasizing the importance of culture-based isolation for characterizing and exploiting oral bacteria.

Long non-coding RNA PFI inhibits apoptosis of alveolar epithelial cells to alleviate lung injury via miR-328-3p/Creb1 axis.

Acute lung injury (ALI), a common clinical type of critical illness, is an acute hypoxic respiratory insufficiency caused by the damage of alveolar epithelial cells and capillary endothelial cells. In a previous study, we reported a novel lncRNA, lncRNA PFI, which could protect against pulmonary fibrosis in pulmonary fibroblasts. The present study demonstrated that lncRNA PFI was downregulated in alveolar epithelial cell of mice injury lung tissues, and further investigated the role of lncRNA PFI in regulating inflammation-induced alveolar epithelial cell apoptosis. Overexpression of lncRNA PFI could partially abrogated bleomycin induced type II AECs injured. Subsequently, bioinformatic prediction revealed that lncRNA PFI might directly bind to miR-328-3p, and further AGO-2 RNA binding protein immunoprecipitation (RIP) assay confirmed their binding relationship. Furthermore, miR-328-3p promoted apoptosis in MLE-12 cells by limiting the activation of the Creb1, a protein correlated with cell apoptosis, whereas AMO-328-3p ablated the pro-apoptosis effect of silencing lncRNA PFI in MLE-12 cells. While miR-328-3p could also ablate the function of lncRNA PFI in bleomycin treated human lung epithelial cells. Enhanced expression of lncRNA PFI reversed the LPS-induced lung injury in mice. Overall, these data reveal that lncRNA PFI mitigated acute lung injury through miR-328-3p/Creb1 pathway in alveolar epithelial cells.

Concise Total Synthesis of (-)-Quinocarcin Enabled by Catalytic Enantioselective Reductive 1,3-Dipolar Cycloaddition of Secondary Amides.

A concise asymmetric total synthesis of (-)-quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3-dipolar cycloaddition reaction of N-heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio-, exo- and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a RhIII -catalyzed C-H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline-pyrrolidine tetracyclic core unit of quinocarcin.