Novel Nano Drug-Loaded Hydrogel Coatings for the Prevention and Treatment of CAUTI.

Catheter-associated urinary tract infection (CAUTI) is a prevalent type of hospital-acquired infection, affecting approximately 15% to 25% of patients with urinary catheters. Long-term use of the catheter can lead to colonization of microorganisms and biofilm formation, and may develop into bacterial CAUTI. However, the frequent replacement of catheters in clinical settings can result in tissue damage, inflammation, ulceration, and additional complications, causing discomfort and pain for patients. In light of these challenges, a novel nanodrug-supported hydrogel coating called NP-AM/FK@OMV-P/H has been developed in this study. Through in vitro experiments, it is confirmed that OMV nano-loaded liquid gel coating has an effective reaction against E.coli HAase and releases antibacterial drugs. This coating has also demonstrated strong inhibition of E.coli and has shown the ability to inhibit the formation of bacterial biofilm. These findings highlight the potential of the OMV nanoparticle gel coating in preventing and treating bacterial infections. Notably, NP-AM/FK@OMV-P/H has exhibited greater efficacy against multidrug-resistant E.coli associated with UTIs compared to coatings containing single antimicrobial peptides or antibiotics. Additionally, it has demonstrated good biosecurity. In conclusion, the NP-AM/FK@OMV-P/H coating holds great potential in providing benefits to patients with CAUTI.

Asthmatic patients with vitamin D deficiency: Can vitamin D supplementation make a difference.

BACKGROUND: Asthma is a major public health concern due to its persistent inflammation of the airways. The intricate and widely variable epidemiology of asthma among nations and populations is a result of the interplay between genetic, environmental, and socioeconomic factors. OBJECTIVE: This study aims to investigate whether VitD supplementation can reduce the frequency of exacerbations (including the frequency of exacerbations requiring systemic corticosteroids and the frequency of exacerbations necessitating trips to the hospital or emergency room, or both) and improve pulmonary function (clinical indicators such as the FEV1% predicted value). METHODS: Computers were used to search Pubmed, Medline, ISI Web of Science, Embase, Cachrane Library, CNKI, CBM, VIP, and the Wanfang Database. Asthma/asthma, VitD/VitD, lung function/lung function, retrieval time is from database setup to October 8, 2021, to search all randomized controlled trials (RCTs) on the effect of VitD on human asthma and to retroactively incorporate references to literature were all included in the search criteria. After rigorous screening, quality evaluation, and data extraction of the included literature by two reviewers independently, heterogeneity tests and sensitivity analyses were performed. RESULTS: The findings show that a total of 12 relevant studies meeting the inclusion criteria were finally included, including 649 cases in the experimental group and 646 cases in the control group. VitD intervention reduced the number of asthma exacerbations, including the rate of exacerbations requiring systemic corticosteroid therapy and the rate of acute exacerbations requiring emergency department or hospital visits or both. CONCLUSIONS: In the outcome of lung function (FEV1% predicted value), it was shown that VitD supplementation improved lung function; in the outcome of serum 25-hydroxyVitD levels, it was shown that VitD supplementation increased serum 25-hydroxyVitD levels.

Sustainable succinic acid production from lignocellulosic hydrolysates by engineered strains of Yarrowia lipolytica at low pH.

Succinic acid (SA) is a valuable C4 platform chemical with diverse applications. Lignocellulosic biomass represents an abundant and renewable carbon resource for microbial production of SA. However, the presence of toxic compounds in pretreated lignocellulosic hydrolysates poses challenges to cell metabolism, leading to inefficient SA production. Here, engineered Yarrowia lipolytica Hi-SA2 was shown to utilize glucose and xylose from corncob hydrolysate to produce 32.6 g/L SA in shaking flasks. The high concentration of undetoxified hydrolysates significantly inhibited yeast growth and SA biosynthesis, with furfural identified as the key inhibitor. Through overexpressing glutathione synthetase encoding gene YlGsh2, the tolerance of engineered strain to furfural and toxic hydrolysate was significantly improved. In a 5-L bioreactor, Hi-SA2-YlGsh2 strain produced 45.34 g/L SA within 32 h, with a final pH of 3.28. This study provides a sustainable process for bio-based SA production, highlighting the efficient SA synthesis from lignocellulosic biomass through low pH fermentation.

Visualized and pH-responsive hydrogel antibacterial coating for ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is a common healthcare-acquired infection often arising during artificial ventilation using endotracheal intubation (ETT), which offers a platform for bacterial colonization and biofilm development. In particular, the effects of prolonged COVID-19 on the respiratory system. Herein, we developed an antimicrobial coating (FK-MEM@CMCO-CS) capable of visualizing pH changes based on bacterial infection and releasing meropenem (MEM) and FK13-a1 in a controlled manner. Using a simple dip-coating process with controlled loading, chitosan was cross-linked with sodium carboxymethyl cellulose oxidation (CMCO) and coated onto PVC-based ETT to form a hydrogel coating. Subsequently, the coated segments were immersed in an indicator solution containing bromothymol blue (BTB), MEM, and FK13-a1 to fabricate the FK-MEM@CMCO-CS coating. In vitro studies have shown that MEM and FK13-a1 can be released from coatings in a pH-responsive manner. Moreover, anti-biofilm and antibacterial adhesion results showed that FK-MEM@CMCO-CS coating significantly inhibited biofilm formation and prevented their colonization of the coating surface. In the VAP rat model, the coating inhibited bacterial growth, reduced lung inflammation, and had good biocompatibility. The coating can be applied to the entire ETT and has the potential for industrial production.

Colon-targeted oral nanoliposomes loaded with psoralen alleviate DSS-induced ulcerative colitis.

Oral administration, while convenient, but complex often faces challenges due to the complexity of the digestive environment. In this study, we developed a nanoliposome (NLP) encapsulating psoralen (P) and coated it with chitosan (CH) and pectin (PT) to formulate PT/CH-P-NLPs. PT/CH-P-NLPs exhibit good biocompatibility, superior to liposomes loaded with psoralen and free psoralen alone. After oral administration, PT/CH-P-NLPs remain stable in the stomach and small intestine, followed by a burst release of psoralen after reaching the slightly alkaline and gut microbiota-rich colon segment. In the DSS-induced ulcerative colitis of mice, PT/CH-P-NLPs showed significant effects on reducing inflammation, mitigating oxidative stress, protecting the integrity of the colon mucosal barrier, and modulating the gut microbiota. In conclusion, the designed nanoliposomes demonstrated the effective application of psoralen in treating ulcerative colitis.

pH- and Matrix Metalloproteinase-Responsive Multifunctional Bilayer Microneedles Platform for Treatment of Tinea Pedis.

Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans. They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by T. mentagrophytes. Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.

CRISPLD1 promotes gastric cancer progression by regulating the Ca2+/PI3K-AKT signaling pathway.

Gastric cancer (GC) is a malignant tumor with poor prognosis. Studies have shown that cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is associated with tumor progression. However, its role in GC is unclear. The present study aimed to determine the pathogenic mechanism of CRISPLD1 in GC. Analysis of public databases revealed high mRNA expression of CRISPLD1 in GC, which was associated with poor prognosis. Additionally, CRISPLD1 expression levels showed significant correlations with T stage, overall survival events, and stage. Knockdown of CRISPLD1 reduced cell proliferation, invasion, and migration. Furthermore, CRISPLD1 knockdown decreased intracellular calcium levels in GC cells and inhibited the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. Treatment with an AKT activator reversed the inhibitory effect of CRISPLD1 knockdown on GC cell migration and invasion. Our findings suggest that CRISPLD1 promotes tumor cell progression in GC by mediating intracellular calcium levels and activating the PI3K-AKT pathway, highlighting CRISPLD1 as a potential therapeutic target for GC.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

Functionalized PLGA Microsphere Loaded with Fusion Peptide for Therapy of Bone Defects.

The challenges in the treatment of extensive bone defects are infection control and bone regeneration. Bone tissue engineering is currently one of the most promising strategies. In this study, a short biopeptide with specific osteogenic ability is designed by fusion peptide technology and encapsulated with chitosan-modified poly(lactic acid-glycolic acid) (PLGA) microspheres. The fusion peptide (FP) mainly consists of an osteogenic functional sequence (P-15) and a bone-specific binding sequence (Asp-6), which can regulate bone formation accurately and efficiently. Chitosan-modified PLGA with antimicrobial and pro-healing effects is used to achieve the sustained release of fusion peptides. In the early stage, the antimicrobial and soft tissue healing effects can stop the wound infection as soon as possible, which is relevant for the subsequent bone regeneration process. Our data show that CS-PLGA@FP microspheres have antibacterial and pro-cell migration effects in vitro and excellent pro-wound-healing effects in vivo. In addition, CS-PLGA@FP microspheres promote the expression of osteogenic-related factors and show excellent bone regeneration in a rat defect model. Therefore, CS-PLGA@FP microspheres are an efficient biomaterial that can accelerate the recovery of bone defects.

Fe-codoped carbon dots serving as a peroxidase mimic to generate in situ hydrogen peroxide for the visual detection of glucose.

Nanozyme technology has gained significant regard and been successfully implemented in various applications including chemical sensing, bio-medicine, and environmental monitoring. Fe-CDs were synthesized and characterized well in this study. As compared to HRP (3.7 mM), the Fe-CDs exhibited a higher affinity towards H2O2 (0.2 mM) using the steady-state kinetic assay and stronger catalytic capability by changing the color of TMB to the blue color of the oxidized state, oxTMB. Additionally, an efficient peroxidase mimic, Fe-CDs/GOx, based on the hybrid cascade system to produce in situ H2O2 for the visual detection of glucose (color change: colorless to blue, and then to green), has been developed in detail, with limits of detection (LODs) for H2O2 and glucose of 0.33 µM and 1.17 µM, respectively. The changes further demonstrate a linear relationship between absorbance and H2O2 concentration, ranging from 10 to 60 µM, and for glucose (1 to 60 µM). To assess the accuracy and detection capability of the Fe-CDs/GOx system, we evaluated a real human serum sample obtained from adult males in a local hospital. In conclusion, Fe-CDs serving as a peroxidase mimic have the potential for various applications in the fields of biomedicine and nanozymes.

TBOPP, a DOCK1 Inhibitor, Potentiates Cisplatin Efficacy in Breast Cancer by Regulating Twist-mediated EMT.

BACKGROUND: DOCK1 has been reported to be involved in tumor progression and resistance. 1-(2-(30-(trifluoromethyl)-[1,10-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl2(1H)- pyridone (TBOPP) is a selective DOCK1 inhibitor; however, the role and molecular mechanisms of DOCK1 and its inhibition in breast cancer (BC) resistance remain poorly understood. OBJECTIVE: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance. METHODS: DOCK1 or Twist siRNA and Twist plasmid were used to explore the function of DOCK1 in vitro experiments. A mouse xenograft model was used for in vivo experiments. RESULTS: In the present study, we demonstrated that DOCK1 siRNA promoted cisplatin sensitivity in BC cells. Moreover, TBOPP also enhances the therapeutic effect of cisplatin both in vitro and in vivo. Mechanistically, DOCK1 siRNA inhibited EMT. Twist 1 is one of the EMT-inducing transcription factors and is known to induce EMT. To further reveal the effect of DOCK in BC cells, we co-transfected with DOCK1 and Twist1 siRNA to BC cells and found that co-transfection with DOCK1 and Twist siRNA could not further enhance the cisplatin sensitivity of BC cells. Moreover, DOCK1 siRNA failed to reverse the effect of Twist 1 up-regulation. CONCLUSION: Taken together, these results demonstrate that DOCK1 may function as a potential therapeutic target in BC and that combining cisplatin with TBOPP may provide a promising therapeutic strategy for cisplatin-resistant BC patients.

BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Effect of safety and security equipment on patient and visitor violence towards nurses in multiple public hospitals of China during the COVID-19 pandemic: a retrospective, difference-in-difference analysis.

OBJECTIVES: This study aimed to analyse whether safety and security equipment decreased patient and visitor violence (PVV) towards nurses in the COVID-19 period and quantify to what extent safety and security equipment affects PVV. DESIGN: Controlled before and after study and difference-in-difference (DID) analysis. SETTING: A large hospital medical group, consisting of three public tertiary teaching hospitals, namely, Xinjiekou Branch, Huilongguan Branch and Xinlongze Branch of Beijing Jishuitan Hospital, located in the west and north parts of Beijing, China. PARTICIPANTS: A panel of nine departments recruited using two-step sampling method, administered online surveys in 2021 and 2022. A total of 632 eligible nurses participated in the survey in 2021 and 725 eligible nurses in 2022. MEASURES: We assessed impacts of the safety and security equipment on the PVV. The policy had been enacted in June 2020, and the corresponding measures were established after mid-December 2020, and therefore, we use a DID design to evaluate changes in nurses' PVV incidence. Departments are classified as either department installed or non installed, and nurses are classified based on their department. RESULTS: Within the treatment group, the incidence of physical PVV significantly decreased from 13.8% in 2020 to 2.0% in 2021. In the control group, the incidence of physical PVV increased from 0.6% in 2020 to 2.7% in 2021. The application of the safety and security equipment decreased the incidence of physical PVV by 13.93% (95% CI: -23.52% to -4.34%). In contrast, no difference was observed between the treatment and control groups for the incidence of psychological PVV (6.23%, 95% CI: -11.56% to 24.02%) and overall PVV (0.88, 95% CI: -20.90% to 22.66%). CONCLUSION: The safety and security equipment reduced the incidence of physical PVV towards nurses. For hospital managers in public hospitals, longer-term strategies roadmap for PVV prevention measures are needed to create a more supportive work environment in employees.

AcMYB10 Involved in Anthocyanin Regulation of 'Hongyang' Kiwifruit Induced via Fruit Bagging and High-Postharvest-Temperature Treatments.

Light and temperature are key factors influencing the accumulation of anthocyanin in fruit crops. To assess the effects of fruit bagging during development and high post-ripening temperature on 'Hongyang' kiwifruit, we compared the pigmentation phenotypes and expression levels of anthocyanin-related genes between bagged and unbagged treatments, and between 25 °C and 37 °C postharvest storage temperatures. Both the bagging and 25 °C treatments showed better pigmentation phenotypes with higher anthocyanin concentrations. The results of the qRT-PCR analysis revealed that the gene expression levels of LDOX (leucoanthocyanidin dioxygenase), F3GT (UDP-flavonoid 3-O-glycosyltransferase ), AcMYB10, and AcbHLH42 were strongly correlated and upregulated by both the bagging treatment and 25 °C storage. The results of bimolecular fluorescence complementation and luciferase complementation imaging assays indicated an interaction between AcMYB10 and AcbHLH42 in plant cells, whereas the results of a yeast one-hybrid assay further demonstrated that AcMYB10 activated the promoters of AcLODX and AcF3GT. These results strongly suggest that enhanced anthocyanin synthesis is caused by the promoted expression of AcLODX and AcF3GT, regulated by the complex formed by AcMYB10-AcbHLH42.

Repurposing endogenous type II CRISPR-Cas9 system for genome editing in Streptococcus thermophilus.

Streptococcus thermophilus has been extensively used in industrial milk fermentation. However, lack of efficient genetic manipulation approaches greatly hampered the industrial application of this species. Here, we repurposed the endogenous CRISPR1 and CRISPR3 systems, both belong to type II-A CRISPR-Cas9, by delivering a self-targeting CRISPR array with DNA repair template into S. thermophilus LMD-9. We achieved 785-bp deletion in lacZ gene by repurposing CRISPR1 and CRISPR3 systems with efficiencies of 35% and 59%, respectively, when 1-kb DNA repair template was provided. While providing with 1.5-kb repair template, the editing efficiency for deletion in lacZ gene reached 90% using CRISPR3 systems. Diverse editing outcomes encompassing a stop code insertion and single nucleotide variation within lacZ, as well as a 234-bp DNA fragment insertion upstream of ster_0903, were generated with high efficiencies of 75%-100% using the CRISPR3 system. Harnessing the customized endogenous CRISPR3 system to target six genes of eps gene cluster, we obtained six single-gene knockout mutants with efficiencies of 29%-80%, and proved that the epsA, epsE, and epsG were the key genes affecting exopolysaccharides biosynthesis in S. thermophilus LMD-9. Altogether, repurposing the native type II-A CRISPR-Cas9 can be served as a toolkit for precise genome engineering in S. thermophilus for biotechnological applications.

Histatin 1-modified SIS hydrogels enhance the sealing of peri-implant mucosa to prevent peri-implantitis.

Dental implants make it possible to replace teeth in more sophisticated ways. Nevertheless, peri-implantitis is one of the leading causes of implant failure, which can be avoided with proper soft tissue sealing. The aim of this study was to achieve the promotion of the synthesis of peri-implant epithelial hemidesmosome through Histatin 1 and porcine small intestinal submucosa (SIS) hydrogel to form a good peri-implant seal. The results show that hydrogel can improve the biological barrier function around implants by combining antibacterial, promoting soft tissue healing and promoting epithelial bonding. This means that the morphology and anti-infection ability of soft tissue are enhanced, which ensures the long-term stability of the implant.SIS-Hst1 hydrogel has certain clinical application in the prevention and early treatment of peri-implantitis. In conclusion, Hst1-SIS hydrogel, as a local administration system, provides experimental evidence for the prevention of peri-implant disease.

Exploring elderly patients' experiences and concerns about early mobilization implemented in postoperative care following lumbar spinal surgery: a qualitative study.

BACKGROUND: Given its apparent benefits, early mobilization is becoming increasingly important in spinal surgery. However, the time point at which patients first get out of bed for mobilization after spinal surgery varies widely. Beginning in January 2022, we conducted a study of early mobilization (mobilization within 4 h postoperatively) following multi-segment lumbar decompression and fusion surgery in elderly patients. The study goal was to better understand elderly patients' perceptions of early mobilization and ultimately contribute to the improvement of elderly patients' perioperative experiences and quality of life. METHODS: We employed a qualitative descriptive study design involving face-to-face semi-structured interviews. Forty-five consecutive patients were invited, among whom 24 were enrolled and completed the qualitative investigation from February to June 2022. Of these 24 patients, 10 underwent early mobilization (mobilization within 4 h postoperatively) and 14 underwent mobilization at ≥ 24 h postoperatively. Three researchers conducted a 15-question interview the day before each patient's discharge. The interviews were audio-recorded, and content analysis was used to assess the data. RESULTS: Six themes regarding the patients' experiences and concerns about early mobilization were identified: worries, benefits, daily routines, pain, education, and support. The study results revealed the obstacles in early mobilization practice and highlighted the importance of perioperative education on early mobilization. CONCLUSIONS: Clear and explicit guidance on early mobilization and a multidisciplinary mobilization protocol that incorporates a comprehensive pain management plan are essential for effective patient education. These measures may have positive effects on reducing patients' stress and anxiety regarding postoperative early mobilization.

Prevalence of frailty among elderly patients with hip fracture in China: protocol for a systematic review and meta-analysis.

INTRODUCTION: Frailty is a clinical syndrome characterised by a reduced ability to adapt to external stressors owing to a reduced physiological reserve, which is caused by degeneration of multiple organ systems. Frailty is particularly prevalent among patients with hip fractures. Research on frailty in China started late; thus, evidence regarding the prevalence of frailty among older patients with hip fracture in China is scarce. The aim of this systematic review and meta-analysis is to systematically search for available data on the prevalence of frailty among older patients with hip fracture in China, assess the pooled prevalence of frailty and describe the association between frailty and clinical outcomes. METHOD AND ANALYSIS: We will systematically search electronic databases, including Web of Science, Embase, PubMed, the Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang data Database, to identify studies on the prevalence of frailty in older patients with hip fracture. Two reviewers will independently identify eligible studies according to defined inclusion criteria and critically appraise them using the Joanna Briggs Institute's standardised critical appraisal tool. Data will be analysed using Stata V.12.0. ETHICS AND DISSEMINATION: Ethics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022265321.

The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4.

PURPOSE: Breast cancer (BC) is the most frequent malignant tumor in women worldwide with exceptionally high morbidity. The RNA-binding protein MEX3A plays a crucial role in genesis and progression of multiple cancers. We attempted to explore its clinicopathological and functional significance in BC in which MEX3A is expressed. METHODS: The expression of MEX3A detected by RT-qPCR and correlated the results with clinicopathological variables in 53 BC patients. MEX3A and IGFBP4 profile data of BC patients were downloaded from TCGA and GEO database. Kaplan-Meier (KM) analysis was used to estimate the survival rate of BC patients. Western Blot, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MEX3A and IGFBP4 in BC cell proliferation, invasion and cell cycle in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of BC cells after MEX3A knockdown. The interactions among MEX3A and IGFBP4 were measured by RNA pull-down and RNA immunoprecipitation. RESULTS: The expression of MEX3A was upregulated in BC tissues compared to adjacent tissues and high expression of MEX3A was associated with poor prognosis. Subsequent in vitro studies demonstrated that MEX3A knockdown inhibited BC cells proliferation and migration, as well as xenograft tumor growth in vivo. The expression of IGFBP4 was significantly negatively correlated with MEX3A in BC tissues. Mechanistic investigation showed that MEX3A binds to IGFBP4 mRNA in BC cells, decreasing IGFBP4 mRNA levels, which further activated the PI3K/AKT and other downstream signaling pathways implicated cell cycle progression and cell migration. CONCLUSION: Our results indicate that MEX3A plays a prominent oncogenic role in BC tumorigenesis and progression by targeting IGFBP4 mRNA and activating PI3K/AKT signaling, which can be used as a novel therapeutic target for BC.

Bacterial genome reduction for optimal chassis of synthetic biology: a review.

Bacteria with streamlined genomes, that harbor full functional genes for essential metabolic networks, are able to synthesize the desired products more effectively and thus have advantages as production platforms in industrial applications. To obtain streamlined chassis genomes, a large amount of effort has been made to reduce existing bacterial genomes. This work falls into two categories: rational and random reduction. The identification of essential gene sets and the emergence of various genome-deletion techniques have greatly promoted genome reduction in many bacteria over the past few decades. Some of the constructed genomes possessed desirable properties for industrial applications, such as: increased genome stability, transformation capacity, cell growth, and biomaterial productivity. The decreased growth and perturbations in physiological phenotype of some genome-reduced strains may limit their applications as optimized cell factories. This review presents an assessment of the advancements made to date in bacterial genome reduction to construct optimal chassis for synthetic biology, including: the identification of essential gene sets, the genome-deletion techniques, the properties and industrial applications of artificially streamlined genomes, the obstacles encountered in constructing reduced genomes, and the future perspectives.