One-stone, two birds: One step regeneration of discarded copper foil in zinc battery for dendrite-free lithium deposition current collector.

The ever-growing requirement for electrochemical energy storage has exacerbated the production of spent batteries, and the recycling of valuable battery components has recently received a remarkable attention. Among all battery components, copper foil is widely utilized as a current collector for stable zinc platting and stripping in zinc metal batteries (ZMBs) due to the perfect lattice matching of between metal copper and zinc, which is accompanied by the formation of multiple copper-zinc alloy components during the cycling process. Herein, a novel "two birds with one-stone" strategy through a one simple heat treatment step to revive the discarded copper foil in zinc metal battery is reported to further obtain a lithiophilic current collector (CuxZny-Cu) with multiple copper-zinc alloy components on the surface of the discarded copper foil. Such revived CuxZny-Cu current collector greatly reduces the lithium nucleation overpotential and realizes uniform lithium deposition and further inhibits lithium dendrites growth. The formed multiple CuxZny alloy phases on the surface of discarded copper foil exhibit a low Li nucleation overpotential of only 15 mV at 0.5 mA cm-2 for the first cycle. Moreover, such a CuxZny-Cu current collector could achieve stable cycle for 220 cycles at 0.5 mA cm-2 and 110 cycles at 1 mA cm-2 with a Li plating capacity of 1 mAh cm-2. Theoretical calculations indicate that, compared with pure Cu foil, the formed multiple alloy components of CuZn5, CuZn8, Cu0.61Zn0.39 and CuZn have low adsorption energy of -2.17, -2.55, -2.16 and -2.35 eV with lithium atoms, respectively, which result in reduced lithium nucleation overpotential. The full cell composed of CuxZny alloy current collector with deposition of 5 mAh cm-2 metal Li anode coupled with LiFePO4 (LFP) cathode exhibits a reversible capacity of 125.6 mAh/g after 110 cycles at a current of 0.5 C with capacity retention of 85.1 %. This work proposed a promising strategy to regenerate the discarded copper foil in rechargeable batteries.

Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.

Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.

Thrombosis density ratio can predict the occurrence of pulmonary embolism and post-thrombotic syndrome in lower-extremity deep vein thrombosis patients.

OBJECTIVE: Deep vein thrombosis (DVT) formation of lower extremities can lead to serious complications including pulmonary embolism (PE) and chronic post-thrombotic syndrome (PTS). We aimed to explore the relationship between the ratio of thrombotic density and the occurrence of PE and PTS in patients with DVT of the lower extremities. METHODS: A retrospective analysis was conducted in patients who performed computed tomography venography, dividing into DVT with PE group (54 patients) and DVT-alone group (34 patients), The clinical data were recorded. Univariate and multivariate logistic regression analysis were used to analysis variables associated with PE. The ability of thrombosis density ratio and Wells score to diagnose PE was evaluated by using the receiver operating characteristic curve (ROC) area under the curve (AUC). According to the treatment and follow-up results, subgroup analysis was performed, and the Villata score was used to determine the presence or absence of PTS and its severity. RESULTS: Compare with the DVT-alone group, more patients had dyspnea and chest pain in the DVT with PE group. DVT with PE group had lower the percentage of neutrophils, white blood cell count and platelet count, while had higher blood cell count, D-dimer, wells score, thrombus and thrombus density ratio. Multivariate logistic analysis showed that percentage of neutrophils (OR(95% CIs)=1.15 (1.01,1.31), P = 0.040), platelets (OR(95% CIs)=0.96 (0.93,0.99), P = 0.011), and thrombus density ratio (OR(95% CIs)=5.99 (1.96,18.35), P = 0.002) are independent predictors of PE. The Wells score and thrombosis density ratio were consistent in the diagnostic efficacy of PE. In the subgroup analysis, there was a relevance between the ratio of thrombosis density and the Villalta score. CONCLUSION: Percentage of neutrophils, platelets, and thrombus density ratio are independent predictors of PE. The thrombosis density of DVT patients may be an index to predict the risk of PE and PTS in DVT patients.

[Effects of Organic Fertilization on Bacterial Community and Maize Productivity in Dryland Red Soil].

Since 2002, a long-term field experiment has been conducted to determine the effects of different organic fertilization treatments on the bacterial community characteristics and maize productivity in dryland red soil using high-throughput sequencing technology. The experiment consisted of four treatments:no manure, M0; low manure, M1; high manure, M2; and high manure with lime addition, M3. Our results showed that the different organic fertilization treatments(M1, M2, and M3) significantly promoted maize productivity with the highest values of pH, soil organic matter(SOM), total nitrogen(TN), and total phosphorus(TP) compared to that under the M0 treatment, and the high manure with lime addition(M3) treatment had the highest level of maize production. The different organic fertilization treatments significantly increased the Shannon index, Evenness index, Chao1 index, and ACE index and significantly shaped the composition of the bacterial community. TP and pH were the main variables determining soil bacterial diversity index based on random forest modeling analysis, whereas pH, SOM, TP, and TN were the main variables determining the structure of the soil bacterial community. Correlation analysis and structural equation modeling determined that TP and SOM indirectly affected maize productivity by varying the bacterial diversity and community structure. The results of this study provide the scientific basis for ensuring food security and sustainable agricultural development by improving the fertility and bacterial diversity in dryland red soil.

HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury.

Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited.

Exosomal MiR-381 from M2-polarized macrophages attenuates urethral fibroblasts activation through YAP/GLS1-regulated glutaminolysis.

OBJECTIVE AND DESIGN: Post-traumatic urethral stricture is a clinical challenge for both patients and clinicians. Targeting glutamine metabolism to suppress excessive activation of urethral fibroblasts (UFBs) is assumed to be a potent and attractive strategy for preventing urethral scarring and stricture. MATERIAL OR SUBJECTS: In cellular experiments, we explored whether glutaminolysis meets the bioenergetic and biosynthetic demands of quiescent UFBs converted into myofibroblasts. At the same time, we examined the specific effects of M2-polarized macrophages on glutaminolysis and activation of UFBs, as well as the mechanism of intercellular signaling. In addition, findings were further verified in vivo in New Zealand rabbits. RESULTS: It revealed that glutamine deprivation or knockdown of glutaminase 1 (GLS1) significantly inhibited UFB activation, proliferation, biosynthesis, and energy metabolism; however, these effects were rescued by cell-permeable dimethyl α-ketoglutarate. Moreover, we found that exosomal miR-381 derived from M2-polarized macrophages could be ingested by UFBs and inhibited GLS1-dependent glutaminolysis, thereby preventing excessive activation of UFBs. Mechanistically, miR-381 directly targets the 3'UTR of Yes-associated protein (YAP) mRNA to reduce its stability at the transcriptional level, ultimately downregulating expression of YAP, and GLS1. In vivo experiments revealed that treatment with either verteporfin or exosomes derived from M2-polarized macrophages significantly reduced urethral stricture in New Zealand rabbits after urethral trauma. CONCLUSION: Collectively, this study demonstrates that exosomal miR-381 from M2-polarized macrophages reduces myofibroblast formation of UFBs and urethral scarring and stricture by inhibiting YAP/GLS1-dependent glutaminolysis.

Patients with MMAF induced by novel biallelic CFAP43 mutations have good fertility outcomes after intracytoplasmic sperm injection.

As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 ( CFAP43 ) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43 , including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43 -deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43 , and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future.

ARPC1A correlates with poor prognosis in prostate cancer and is up-regulated by glutamine metabolism to promote tumor cell migration, invasion and cytoskeletal changes.

OBJECTIVE: This study aimed to identify potential biomarkers for prostate cancer (PCa) progression and metastasis, and to discern their biological functions. METHODS: Bioinformatics methods were used to screen for hub genes. The expression level of key hub genes in PCa was determined and their prognostic significance was examined. A series of functional assays were performed to investigate the function of the highest-ranking hub gene. RESULTS: Actin related protein 2/3 complex subunit 1A (ARPC1A) was identified as the hub gene. ARPC1A was highly expressed in PCa tissues and cell lines, and was an independent prognostic factor for predicting biochemical recurrence after radical prostatectomy and overall survival of PCa patients. Knockdown of ARPC1A inhibited PCa cell migration, invasion and cytoskeleton formation, but had no impact on cell proliferation and cell cycle progression. In vivo, ARPC1A overexpression promoted lung metastasis of PCa, but had no efffect on tumor growth. Additionally, glutamine metabolism was identified as an upstream regulator of ARPC1A, and promoted migration, invasion and cytoskeletal changes of PCa cell through ARPC1A. CONCLUSION: These findings suggested that ARPC1A, which correlates with poor prognosis in PCa, functions downstream of glutamine metabolism to regulate cytoskeletal changes, cellular migration and cellular invasion in this disease.

Comparison of biological behavior of lacrimal gland adenoid cystic carcinoma with high-grade transformation cells.

AIM: To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation (LACC-HGT) primary cells cultured by high-grade transformation tissue and non-high-grade transformation (non-HGT) primary cells cultured by non-high-grade transformation tissue in proliferation, metastasis, drug susceptibility, and genes. METHODS: LACC-HGT primary cells were established by tissue block culture, and the 4th to 10th generation primary cells were selected as research objects. The cells were preliminarily identified by immunofluorescent staining. The differences between non-HGT and LACC-HGT primary cells in terms of proliferation, metastasis, and drug susceptibility were compared by cell counting kit-8 (CCK-8) assay, wound healing, and drug sensitivity experiments. Differentially expressed genes were screened using mRNA array. Gene expression was analyzed using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: LACC-HGT primary cells were successfully cultured by tissue block culture. Immunofluorescence staining results showed that cytokeratin (CK) and CK7 expression levels were positive in LACC-HGT primary cells. CCK-8 results showed that the proliferation ability of LACC-HGT cells was significantly higher than that of non-HGT cells. Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells. LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells. Compared with non-HGT cells, 9566 differentially expressed genes were found in LACC-HGT primary cells, of which 5162 were up-regulated and 4404 were down-regulated. The expression of N-acetylneuraminate pyruvate lyase (NPL), MARVEL domain containing 3 (MARVELD3), syntabulin (SYBU), and allograft inflammatory factor 1 (AIF1) was higher in LACC-HGT cells than in non-HGT cells, whereas that of periostin (POSTN) was lower. CONCLUSION: LACC-HGT primary cells have faster proliferation, stronger migration ability, and poorer sensitivity to chemotherapy drugs than non-HGT primary cells. The expression of mRNAs in non-HGT and LACC-HGT primary cells are significantly different. These features are speculated to be the reasons why high-grade transformation tissues exhibit higher malignant degree and poorer prognosis than their counterparts.

Risk factors for the postoperative bladder neck contracture in patients with small-volume prostatic hyperplasia.

OBJECTIVE: This study was to explore the risk factors for postoperative bladder neck contracture (BNC) after transurethral operation of prostate in patients with small-volume prostatic obstruction. METHODS: Clinicopathologic data at our center from February 2016 to January 2020 were retrospectively collected and analyzed. Clinicopathological characteristics between patients with and without BNC were compared. Multivariate logistic regression was used to determine the risk factors for postoperative BNC. RESULTS: There were a total of 39 patients (8.53%) with postoperative BNC. Multivariate logistic regression analysis demonstrated that preoperative bladder neck diameter (BND), intravesical prostatic protrusion (IPP), surgical methods (transurethral resection of prostate (TURP)/anatomical endoscopic enucleation of the prostate (AEEP)), and postoperative urinary tract infection (UTI) were independent risk factors for postoperative BNC in patients with small-volume prostatic obstruction (P < 0.05). The incidence of postoperative BNC in patients undergoing AEEP was significantly decreased compared with those undergoing TURP. The optimal cut-off value of preoperative IPP was 6.10 mm while the optimal cut-off value of preoperative BND was 2.52 cm. CONCLUSIONS: Larger preoperative bladder neck and higher preoperative IPP lead to decreased incidence of postoperative BNC in patients with small-volume prostatic obstruction. Active management of postoperative UTI could effectively prevent the occurrence of postoperative BNC. Compared with TURP, complete AEEP would contribute to reduce BNC in patients with small-volume prostatic obstruction.

Effects of Bedaquiline on Antimicrobial Activity and Cytokine Secretion of Macrophages Infected with Multidrug-Resistant Mycobacterium tuberculosis Strains.

Background: Bedaquiline (Bdq) exerts bactericidal effects against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains, including multidrug-resistant M. tuberculosis strains (MDR-MTBs). However, few reported investigations exist regarding Bdq effects on MDR-MTBs-infected macrophages activities and cytokine secretion. Here, Bdq bactericidal activities against MDR-MTBs and related cellular immune mechanisms were explored. Methods: Macrophages infected with MDR-MTBs or H37Rv received Bdq treatments (4 h/8 h/24 h/48 h) at 1 × the minimum inhibitory concentration (1 × MIC), 10 × MIC and 20 × MIC. Intracellular colony-forming units (CFUs) and culture supernatant IL-12/23 p40, TNF-α, IL-6, and IL-10 were determined using the Luminex® 200TM system. Normally distributed continuous data (mean ± standard deviation) were analyzed using t-test or F-test (SPSS 25.0, P < 0.05 deemed statistically significant). Results: (1) 100% of Bdq-treated macrophages (all doses applied over 4-48 h) survived with 0% inhibition of proliferation observed. (2) Intracellular CFUs of Bdq-treated MDR-MTBs-infected macrophages decreased over 4-48 h of treatment, were lower than preadministration and control CFUs, decreased with increasing Bdq dose, and resembled H37Rv-infected group CFUs (48 h). (3) For MDR-MTBs-infected macrophages (various Bdq doses), IL-12/23 p40 levels resembled preadministration group levels and exceeded controls (4 h); TNF-α levels exceeded preadministration group levels (24 h/48 h) and controls (24 h); IL-12/23 p40 and TNF-α levels resembled H37Rv-infected group levels (4 h/8 h/24 h/48 h); IL-6 levels exceeded preadministration and H37Rv-infected group levels (24 h/48 h) and controls (24 h); IL-10 levels resembled preadministration and H37Rv-infected group levels (4 h/8 h/24 h/48 h) and were lower than controls (24 h/48 h); IL-12/23 p40 and IL-10 levels remained unchanged as intracellular CFUs changed, with IL-12/23 p40 levels exceeding controls (4 h) and IL-10 levels remaining lower than controls (24 h/48 h); TNF-α and IL-6 levels increased as intracellular CFUs decreased (24 h/48 h) and exceed controls (24 h). Conclusion: Bdq was strongly bactericidal against intracellular MDR-MTBs and H37Rv in a time-dependent, concentration-dependent manner. Bdq potentially exerted immunomodulatory effects by inducing high-level Th1 cytokine expression (IL-12/23 p40, TNF-α) and low-level Th2 cytokine expression (IL-10).

Role of Platelet to Lymphocyte Ratio and Red Cell Distribution Width in Predicting Postoperative Complications in Patients with Acute Mesenteric Ischemia.

BACKGROUND: The predictive values of the platelet to lymphocyte ratio (PLR) and red cell distribution width (RDW) have been demonstrated in different types of abdominal surgery. The aim of this study was to investigate the interest of the preoperative PLR and RDW as predictors of 30-day postoperative complications in patients with acute mesenteric ischemia (AMI). METHODS: Clinical data of 105 AMI patients were retrospectively reviewed. Postoperative complications were evaluated by the Clavien-Dindo classification. The cutoff values for neutrophil to lymphocyte ratio (NLR), PLR, and RDW were determined by receiver operating characteristic curves. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. RESULTS: In the univariate analyses, advanced age, female, anemia, high white blood cell (WBC), high PLR, high NLR, high RDW, Charlson comorbidity index (CCI) score ≥2, and bowel resection were associated with the postoperative complications. A multivariable analysis revealed that advanced age, high PLR, high RDW, and bowel resection were independent predictors of postoperative complications. CONCLUSIONS: The PLR and RDW might play important roles in evaluation of the risk of postoperative complications in AMI patients. The preoperative PLR and RDW are simple and useful predictors of postoperative complications in AMI patients.

The psoas muscle density as a predictor of postoperative complications and 30-day mortality for acute mesenteric ischemia patients.

OBJECTIVE: Low muscle mass and quality is associated with poor surgical outcomes. Psoas muscle density (PMD)is a validated surrogate for muscle quality that can be easily measured from a clinical computed tomography (CT) scan. The objective of this study was to investigate the association between PMD and short-term postoperative outcomes in patients with acute mesenteric ischemia (AMI). METHODS: From April 2006 and September 2019, the clinical data of all patients who underwent surgical intervention with a preoperative diagnosis of AMI and had preoperative non-contrast CT images available were retrospectively reviewed. PMD was measured by CT at the third lumbar vertebra. The lowest quartile of PMD for men and women in all patients was used as sex-specific cut-off values for low PMD. Univariate and multivariate analyses evaluating risk factors of postoperative complications and 30-day mortality were performed. RESULTS: The cohort consisted of 88 patients with a mean age of 58.8 ± 16.2 years, of whom 21 (23.9%) patients had low PMD based on the diagnostic cut-off values (40.5 HU for men and 28.4 HU for women), 35 (39.8%) patients developed complications within 30 days of the operation, and 10 (11.3%) patients died within 30 days of surgery. Low PMD patients had a higher risk of postoperative complications and 30-day mortality than patients without low PMD patients. In a multivariate analysis, low PMD and low psoas muscle area (PMA) were independent predictors of postoperative complications. However, only low PMD remained an independent risk factor for 30-day mortality. CONCLUSIONS: Preoperative assessment of the PMD on CT can be a practical method for identifying AMI patients at risk for postoperative complications and 30-day mortality.

Feasibility of Predicting Pelvic Lymph Node Metastasis Based on IVIM-DWI and Texture Parameters of the Primary Lesion and Lymph Nodes in Patients with Cervical Cancer.

RATIONALE AND OBJECTIVES: To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer. MATERIALS AND METHODS: A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances. RESULTS: In primary lesions study, model 1 was constructed by combining f value, original_shape_Sphericity and original_firstorder_Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original_glszm_Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively. CONCLUSION: Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance.

[Influence of prostatic calculi on the results of prostate biopsy in patients with a PSA level of 4－10 µg/L].

OBJECTIVE: To investigate the influence of prostatic calculi on the results of prostate biopsy in patients with a PSA level of 4－10 µg/L. METHODS: We reviewed the clinical data on 317 patients with a PSA level of 4－10 µg/L on prostate biopsy performed in The First Affiliated Hospital of Fujian Medical University between May 2012 and May 2019, concerning age, body mass index (BMI), prostate volume, PSA level, FPSA/TPSA ratio, PSA density (PSAD), scores on Prostate Imaging Reporting and Data System version 2 (PI-RADS), prostatic calculi and pathological findings. Using logistic regression analysis and ROC curves, we evaluated the influence of prostatic calculi on the results of prostate biopsy. RESULTS: Multivariate analysis showed that age and the PI-RADS score were independent risk factors of positive prostate biopsy, while the prostate volume, FPSA/TPSA ratio and calculus burden were independent protective factors, and that the PI-RADS score was an independent risk factor of clinically significant PCa, while calculus burden and FPSA/TPSA ratio were independent protective factors. Subgroup analysis of the prostatic calculi revealed that the rates of positive prostate biopsy and clinically significant PCa were higher in the patients with calculi in the peripheral zone than in the other groups, but lower in those with calculi in the central or transitional zone than in the peripheral zone and non-calculus groups. CONCLUSIONS: The rates of positive prostate biopsy and clinically significant PCa are low in prostatic calculus patients with a PSA level of 4－10 µg/L, especially in those with calculi in the central or transitional zone.

COVID-19 Lockdown Increased the Risk of Preterm Birth.

Purpose: To estimate whether the city-specific lockdown in Shanghai induced by the COVID-19 pandemic affected preterm birth rates among uninfected pregnant women in different trimesters. Methods: The population-based retrospective cohort study was conducted in the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai, China. Pregnant women without COVID-19 received perinatal healthcare during lockdown (from January 24, 2020 to March 24, 2020) and non-lockdown (from January 24, 2019 to March 24, 2019) period and giving birth to a live infant at IPMCH were enrolled. 1:1 propensity score matching and Inverse probability of treatment weighting were used to evaluate preterm birth (<37 weeks), very preterm birth (<34 weeks), preterm birth with premature rupture of membranes (PROM-PTB), spontaneous preterm birth with intact membranes (S-PTB), and medically induced preterm birth (MI-PTB) between two groups. Results: 8,270 pregnant women were in the lockdown group, and 9,815 were in the non-lockdown group. Pregnant women in second trimester during lockdown had a higher risk of PTB than those during the non-lockdown period [OR: 1.43 (CI 1.01-2.02), ARD: 1.7% (CI 0.04-3.4%), p = 0.045]. Furthermore, pregnant women in third trimester during lockdown had a higher risk of PROM-PTB than those during the non-lockdown period [OR: 1.64 (CI 1.09-2.47), ARD: 0.9% (CI 0.2-1.6%), p = 0.02]; no group differences were found related to rates of VPTB, S-PTB or MI-PTB. Conclusion: In this cohort study in China, we found that there was an increased risk in preterm birth for non-infected women in COVID-19 lockdown who were in their second trimester.

Development and Validation of Novel Biomarkers Related to M2 Macrophages Infiltration by Weighted Gene Co-Expression Network Analysis in Prostate Cancer.

M2-tumor-associated macrophages (TAMs) work as a promoter in the processes of bone metastases, chemotherapy resistance, and castration resistance in prostate cancer (PCa), but how M2-TAMs affect PCa has not been fully understood. In this study, we analyzed the proportion of tumor-infiltrating immune cells using the CIBERSORT algorithm, based on samples from the Cancer Genome Atlas database. Then we performed weighted gene co-expression network analysis to examine the modules concerning infiltrated M2-TAMs. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was constructed. The International Cancer Genomics Consortium cohort was used as a validation cohort. The red module showed the most correlation with M2-TAMs in PCa. Biological processes and pathways were mainly associated with the immune-related processes, as revealed by functional annotation. Four hub genes were screened: ACSL1, DLGAP5, KIF23 and NCAPG. Further validation showed that the four hub genes had a higher expression level in tumor tissues than that in normal tissues, and they were good prognosis biomarkers for PCa. In conclusion, these findings contribute to understanding the underlying molecular mechanisms of how M2-TAMs affect PCa, and looking for the potential biomarkers and therapeutic targets for PCa patients.

Mesenchymal Stem Cell-Derived Exosomes Induced by IL-1ß Attenuate Urethral Stricture Through Let-7c/PAK1/NF-κB-Regulated Macrophage M2 Polarization.

BACKGROUND: Urethral stricture is a clinical challenge for both patients and clinicians. Post-traumatic urethral stricture is associated with formation of scar tissue caused by excessive inflammation. The aim of this study is exploring potential therapeutic strategies for this condition. METHODS: In vivo experiments on New Zealand rabbits and in vitro experiments on THP-1 monocytes and urethral fibroblasts were performed to investigate the effects on post-traumatic urethral stricture of exosomes isolated from IL-1ß-treated mesenchymal stem cells (Exo-MSCsIL-1ß) and the role of macrophage M2 polarization in this process. Additionally, related signaling and mechanism behind were explored. RESULTS: In a New Zealand rabbit model of post-traumatic urethral stricture, injection of Exo-MSCsIL-1ß significantly reduced urethral stricture and collagen fiber accumulation compared with Exo-MSCs. Addition of Exo-MSCsIL-1ß to THP-1 monocytes in vitro induced M2 macrophage polarization, which, in turn, inhibited activation of urethral fibroblasts and synthesis of collagen. Mechanistically, Exo-MSCsIL-1ß were found to contain high levels of the microRNA let-7c, and luciferase reporter assays showed that let-7c interacted with the 3'UTR of PAK1 mRNA. Transfection of THP-1 cells with a let-7c mimic downregulated PAK1 expression and inhibited activation of the NF-κB signaling pathway. CONCLUSION: These results support a role for let-7c-containing Exo-MSCsIL-1ß in reducing urethral stricture via inhibition of PAK1-NF-κB signaling, M2 macrophage polarization, and differentiation of urethral myofibroblasts.