Engineering Microorganisms for Cancer Immunotherapy.

Cancer immunotherapy presents a promising approach to fight against cancer by utilizing the immune system. Recently, engineered microorganisms have emerged as a potential strategy in cancer immunotherapy. These microorganisms, including bacteria and viruses, can be designed and modified using synthetic biology and genetic engineering techniques to target cancer cells and modulate the immune system. This review delves into various microorganism-based therapies for cancer immunotherapy, encompassing strategies for enhancing efficacy while ensuring safety and ethical considerations. The development of these therapies holds immense potential in offering innovative personalized treatments for cancer.

Construction and mechanism analysis of flame-retardant, energy-storage and transparent bio-based composites based on natural cellulose template.

With the proposal of sustainable development strategy, bio-based energy storage transparent wood (TW) has shown broad application value in green buildings, cold chain transportation, and optoelectronic device fields. However, its application in most fields is limited due to its own flammability. In this study, epoxy resin, triethyl phosphate (TEP) and polyethylene glycol (PEG) were introduced into delignified balsa wood template by vacuum pressure impregnation, and bio-based TW/PEG/TEP integrating flame retardant, high strength and phase-change energy-storage performance was prepared. TW/PEG composites have no leakage during phase change process and their transparency is up to 95 %. Compared with TW/PEG, the shielding effect of char layer and the inhibition effect in condensed and gas phase significantly decrease the total heat release of TW/PEG/TEP. TW/PEG/TEP biocomposites still maintained a high enthalpy of phase change and a low peak melting temperature, which was conducive to its application around the area of low temperature phase change energy storage. In addition, the tensile strength of TW/PEG/TEP was nearly 4 times higher than that of DW, and its toughness was obviously enhanced. TW/PEG/TEP biocomposites conformed to the current concept of energy-saving and green development. It has the potential to replace traditional petrochemical-based materials and shows excellent application prospects in emerging fields.

FRP-XGBoost: Identification of ferroptosis-related proteins based on multi-view features.

Ferroptosis represents a novel form of programmed cell death. Pan-cancer bioinformatics analysis indicates that identifying and modulating ferroptosis offer innovative approaches for preventing and treating diverse tumor pathologies. However, the precise detection of ferroptosis-related proteins via conventional wet-laboratory techniques remains a formidable challenge, largely due to the constraints of existing methodologies. These traditional approaches are not only labor-intensive but also financially burdensome. Consequently, there is an imperative need for the development of more sophisticated and efficient computational tools to facilitate the detection of these proteins. In this paper, we presented a XGBoost and multi-view features-based machine learning prediction method for predicting ferroptosis-related proteins, which was referred to as FRP-XGBoost. In this study, we explored four types of protein feature extraction methods and evaluated their effectiveness in predicting ferroptosis-related proteins using six of the most commonly used traditional classifiers. To enhance the representational power of the hybrid features, we employed a two-step feature selection technique to identify the optimal subset of features. Subsequently, we constructed a prediction model using the XGBoost algorithm. The FRP-XGBoost achieved an accuracy of 96.74 % in 10-fold cross-validation and a further accuracy of 91.52 % in an independent test. The implementation source code of FRP-XGBoost is available at https://github.com/linli5417/FRP-XGBoost.

Unilateral levator avulsion increases the risk of de novo stress urinary incontinence after cystocele repair.

INTRODUCTION: Patients without concurrent baseline stress urinary incontinence (SUI) can develop de novo SUI after transvaginal mesh surgery (TVM) for cystocele repair. Surgeons should be aware of de novo SUI risk factors after TVM. METHODS: A total of 1124 women who were underwent TVM surgeries were recruited and assessed for eligibility from January 1, 2012 to April 30, 2021. All data related to patients and surgeries was collected, which included general conditions, clinical examination, surgery records, and follow-up results. Patients were divided into three groups according to follow-up results and data were compared with each group. The relative risk (RR) of de novo SUI with levator avulsion was also calculated. RESULTS: Three hundred thirty-six patients were included in this study. They were divided into no complication group (n = 249), de novo SUI group (n = 68), and other complications group (n = 19). It seemed elder or obese women had a higher risk of de novo SUI after TVM (p < 0.05). In de novo SUI group, incidence of levator avulsion before surgery were higher than the other two groups (p = 0.001). TVM can significantly change a prolapse to point Aa and Ba on POP-Q quantification system (p < 0.05). RR ratios of de novo SUI with unilateral avulsion group is 2.60 (95% confidence interval [CI] 1.39-4.87), and 2.58 (95%CI 0.82-8.15) for bilateral group. CONCLUSION: Unilateral levator avulsion, instead of bilateral levator avulsion, is a risk factor of de novo SUI after cystocele repair surgery.

Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA.

Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance.

CLDN4 as a Novel Diagnostic and Prognostic Biomarker and Its Association with Immune Infiltrates in Ovarian Cancer.

Ovarian cancer (OC) is the seventh most prevalent type of cancer in women and the second most common cause of cancer-related deaths in women worldwide. Because of the high rates of relapse, there is an immediate and pressing need for the discovery of innovative sensitive biomarkers for OC patients. Using TCGA and GSE26712 datasets, we were able to identify 17 survival-related DEGs in OC that had differential expression. CLDN4 was the gene that caught our attention the most out of the 17 important genes since its expression was much higher in OC samples than in nontumor samples. The findings of the ROC assays then confirmed the diagnostic utility of the test in screening OC specimens to differentiate them from nontumor specimens. Patients with high CLDN4 expression predicted a shorter overall survival (OS) and disease-specific survival (DSS) than those with low CLDN4 expression, according to clinical research. Patients with low CLDN4 expression predicted longer OS and DSS. Analysis using both univariate and multivariate techniques revealed that CLDN4 expression was an independent factor associated with a poor prognosis for OS and DSS. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram suggested an effective predictive performance for OC patients. After that, we investigated whether or not there was a link between the infiltration of immune cells and the expression of the CLDN4 gene. We found that the expression of CLDN4 was positively associated with Th17 cells, NK CD56bright cells, while negatively associated with Th2 cells, pDC, and T helper cells. In the end, we carried out RT-PCR on our cohort and confirmed that the level of CLDN4 expression was noticeably elevated in OC specimens in comparison to nontumor tissues. The diagnostic usefulness of CLDN4 expression for OC was also validated by the findings of ROC tests. Thus, our findings revealed that CLDN4 may serve as a predictive biomarker in OC to assess both the clinical outcome of OC patients and the level of immune infiltration.

Effect of anterior vaginal wall prolapse repair by modified transvaginal mesh surgery: a retrospective cohort study.

OBJECTIVE: To explore clinical outcomes and complications of modified Transvaginal mesh (M-TVM) for advanced anterior vaginal wall prolapse in 1 year follow-up. METHODS: 574 patients underwent TVM surgeries from 2019 to 2020 were collected and divided into TVM group and M-TVM group, all preoperative and postoperative data was obtained and compared between the two groups. RESULTS: 285 women were involved eventually, including 181 in TVM group and 104 in M-TVM group. No significant difference of general conditions was found between these two groups. After long-term follow-up, patients in TVM group were more likely to suffer from pelvic pain than M-TVM group (P = 0.046). Meshes seemed much wider in M-TVM group (4.5 ± 0.69 cm) than in TVM group (3.0 ± 0.91 cm). No matter TVM or M-TVM, surgeries can significantly change point Aa and Ba when compared to preoperative data. Compared to TVM group, point C and D were significant changed in patients in M-TVM group after surgery (P < 0.001) CONCLUSION: M-TVM is a commendable procedure that can significant correct anterior prolapse with mesh extended wider, and also supply stable apical support at the same time.

pH-Responsive wound dressings: advances and prospects.

Wound healing is a complex and dynamic process, in which the pH value plays an important role in reflecting the wound status. Wound dressings are materials that are able to accelerate the healing process. Among the multifunctional advanced wound dressings developed in recent years, pH-responsive wound dressings, especially hydrogels, show great potential owing to their unique properties of adjusting their functions according to the wound conditions, thereby allowing the wound to heal in a regulated manner. However, a comprehensive review of pH-responsive wound dressings is lacking. This review summarizes the design strategies and advanced functions of pH-responsive hydrogel wound dressings, including their excellent antibacterial properties and significant pro-healing abilities. Other advanced pH-responsive materials, such as nanofibers, composite films, nanoparticle clusters, and microneedles, are also classified and discussed. Next, the pH-monitoring functions of pH-responsive wound dressings and the related pH indicators are summarized in detail. Finally, the achievements, challenges, and future development trends of pH-responsive wound dressings are discussed.

Preparation and Mechanism of Toughened and Flame-Retardant Bio-Based Polylactic Acid Composites.

As a biodegradable thermoplastic, polylactic acid (PLA) shows great potential to replace petroleum-based plastics. Nevertheless, the flammability and brittleness of PLA seriously limits its use in emerging applications. This work is focused on simultaneously improving the flame-retardancy and toughness of PLA at a low additive load via a simple strategy. The PLA/MKF/NTPA biocomposites were prepared by incorporating alkali-treated, lightweight, renewable kapok fiber (MKF) and high-efficiency, phosphorus-nitrogenous flame retardant (NTPA) into the PLA matrix based on the extrusion-injection molding method. When the additive loads of MKF and NTPA were 0.5 and 3.0 wt%, respectively, the PLA/MKF/NTPA biocomposites (PLA3.0) achieved a rating of UL-94 V-0 with an LOI value of 28.3%, and its impact strength (4.43 kJ·m-2) was improved by 18.8% compared to that of pure PLA. Moreover, the cone calorimetry results confirmed a 9.7% reduction in the average effective heat of combustion (av-EHC) and a 0.5-fold increase in the flame retardancy index (FRI) compared to the neat PLA. NTPA not only exerted a gas-phase flame-retardant role, but also a condensed-phase barrier effect during the combustion process of the PLA/MKF/NTPA biocomposites. Moreover, MKF acted as an energy absorber to enhance the toughness of the PLA/MKF/NTPA biocomposites. This work provides a simple way to prepare PLA biocomposites with excellent flame-retardancy and toughness at a low additive load, which is of great importance for expanding the application range of PLA biocomposites.

Comparison of Different Laparoscopic Sacropexy Procedures for Advanced Uterine Prolapse: A Retrospective Analysis.

STUDY OBJECTIVE: To compare the long-term outcomes and complications of 3 different variants of laparoscopic sacropexy. DESIGN: Single-center retrospective cohort study. SETTING: A tertiary university hospital. PATIENTS: A total of 483 patients with advanced uterine prolapse who underwent laparoscopic sacrohysteropexy (LSH), laparoscopic supracervical hysterectomy with concomitant laparoscopic sacrocervicopexy (LSCH + LSC), or total laparoscopic hysterectomy with concomitant laparoscopic sacrocolpopexy (TLH + LSC). INTERVENTIONS: Demographic data, Pelvic Organ Prolapse Quantification scores, questionnaire results, surgical conditions, postoperative outcomes, and complications were all extracted from medical and follow-up records. MEASUREMENTS AND MAIN RESULTS: Between April 2012 and December 2020, 277 women underwent LSH, 95 women underwent LSCH + LSC, and 111 women underwent TLH + LSC. LSH procedures were associated with statistically significantly least blood loss and least postoperative hospital days and catheterization days (all p <.001). During the median follow-up of 32 months (13-117 months), analysis of the data revealed notable anatomic correction in all groups regarding Pelvic Organ Prolapse Quantification measurements (p <.001), and the anatomic cure rate showed no significant difference among these 3 groups (p = .273). No statistically significant differences were detected for prolapse recurrence (p = .171) and functional improvements among these groups. Neither intraoperative injuries (p = .098) nor total postoperative complications (p = .218) differed considerably, whereas the rate of severe postoperative complications (p <.001) including mesh exposure (p = .004) was significantly higher in the TLH + LSC group than that in the other groups. CONCLUSIONS: LSH is the appropriate choice for women with uterine prolapse without contraindications for uterine preservation. For patients with benign uterine lesions and a normal cervix, LSCH + LSC is a safer approach that provides similar anatomic results and improved quality of life scores that are similar to those of TLH + LSC. For patients with lesions in the uterus and cervix, TLH + LSC should be selected.

Hysteroscopic management of a "hernia-like" uterine myoma within the uterine cavity.

OBJECTIVE: To introduce a case of a uterus "hernia-like" myoma within the uterine cavity that was successfully treated with hysteroscopy. DESIGN: Step-by-step explanation of the case and surgical procedure using a video and slides. The Medical Ethics Committee of Women and Children's Hospital of Chongqing Medical University approved the study and decided for this video to be exempt from formal approval, and informed consent was obtained from the patient. SETTING: Hospital. PATIENT(S): A 37-year-old woman, gravida 1, para 1, with a history of secondary infertility for 2 years and heavy menstrual bleeding for 7 months, which eventually resulted in anemia, was diagnosed with a type 1 (International Federation of Gynecology and Obstetrics leiomyoma subclassification system) myoma approximately 4 cm in diameter using ultrasonography. Her hemoglobin level was 8.6 g/dL (11.5-15.0 g/dL), red blood cell count was 3.6 ×10-12/L (3.8-5.1 ×10-12/L), and hematocrit was 26.7% (35%-45%). INTERVENTION(S): Hysteroscopic myomectomy with bipolar resectoscope and transabdominal ultrasound guidance was used to resect the hernia-like myoma. Blunt dissection combined with oxytocin (20 U I.V.) and uterine dilation pressure reduction was used to induce the hernial content (myoma) protrusion into the uterine cavity. MAIN OUTCOME MEASURE(S): The hernia-like myoma was completely resected by hysteroscopy, and all symptoms disappeared. RESULT(S): The hernia-like myoma was successfully and completely resected by hysteroscopy. The operative time was 37 minutes. No surgical-related or anesthesia-related complications occurred. During the follow-up period, the patient had regular menstrual cycles without hypermenorrhea, and her anemia had improved. The 5-month follow-up ultrasound examination and hysteroscopy revealed that the uterine cavity had recovered well. The patient conceived 7 months after the procedure and delivered at term (39 weeks 1 day) via cesarean section. CONCLUSION(S): A hernia-like myoma covered with endometrium is a degenerative myoma that herniates into the myometrium and forms a hernia sac-like defect. Hysteroscopy is an effective and feasible method for treating hernia-like myoma.

The Role of Gap Junctions in the Generation of Smooth Muscle Cells from Bone Marrow Mesenchymal Stem Cells.

Background: Studies have shown that stem cell transplantation can improve smooth muscle cell (SMC) regeneration and remodelling. Gap junctions can enhance the cytoprotective effects of neighbouring cells. We investigated the effect of gap junctions on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. Materials and Methods: Rat BMSCs and SMCs were obtained from the bone marrow and bladder of Sprague-Dawley rats, respectively. Flow cytometry and multilineage differentiation were performed to assess the characteristics of these cells. BMSCs and SMCs were incubated together in cocultures in the presence and absence of heptanol, an uncoupler of gap junctions. Cocultures were divided into three groups consisting of a contact coculture, noncontact coculture, and contact coculture plus heptanol groups. The expression of BMSC-specific markers and the effect of gap junctions on the differentiation of BMSCs were evaluated by performing real-time reverse transcription-polymerase chain reaction, immunofluorescence analysis, and western blotting after cocultures. Results: CD90 and CD44 were markedly expressed, and CD31 and CD45 were weakly or not expressed in BMSCs. The cells also showed good osteogenic and adipogenic differentiation ability. Compared with the noncontact coculture group, the SMC markers such as α-SMA, calponin, and connexin43 increased in the contact coculture group. The effect of contact in the coculture group was significantly weakened by heptanol. Conclusions: The results suggested that gap junctions play an important role in the generation of SMCs from BMSCs. The formation of SMCs can potentially be used to repair the sphincter muscle of patients with stress urinary incontinence.

Cell membrane-camouflaged inorganic nanoparticles for cancer therapy.

Inorganic nanoparticles (INPs) have been paid great attention in the field of oncology in recent past years since they have enormous potential in drug delivery, gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), bio-imaging, driven motion, etc. To overcome the innate limitations of the conventional INPs, such as fast elimination by the immune system, low accumulation in tumor sites, and severe toxicity to the organism, great efforts have recently been made to modify naked INPs, facilitating their clinical application. Taking inspiration from nature, considerable researchers have exploited cell membrane-camouflaged INPs (CMCINPs) by coating various cell membranes onto INPs. CMCINPs naturally inherit the surface adhesive molecules, receptors, and functional proteins from the original cell membrane, making them versatile as the natural cells. In order to give a timely and representative review on this rapidly developing research subject, we highlighted recent advances in CMCINPs with superior unique merits of various INPs and natural cell membranes for cancer therapy applications. The opportunity and obstacles of CMCINPs for clinical translation were also discussed. The review is expected to assist researchers in better eliciting the effect of CMCINPs for the management of tumors and may catalyze breakthroughs in this area.

A new treatment of an intravesical eroded mesh after TVM: 3 mm trocar-assisted cystoscopic approach.

INTRODUCTION AND HYPOTHESIS: To present a novel technique to remove intravesical eroded mesh through a 3-mm trocar-assisted cystoscopy. METHODS: First, a 3-mm trocar was inserted into the bladder under ultrasound guidance after the bladder had been infused with 600 ml normal saline. Second, we inserted the forceps through the trocar into the bladder and pulled the mesh through the 3-mm trocar. Last, cystoscopic scissors were used to remove the eroded mesh completely. RESULTS: The patient was managed adequately in the inpatient department. The urethral catheter was left in situ for 3 days, and the patient was discharged within 5 days. CONCLUSION: Surgery under 3-mm trocar-assisted cystoscopy offers the advantage of lower risk of morbidity and complications compared to other surgical techniques. It is an effective and feasible procedure for treatment of synthetic mesh erosion into the bladder after TVM surgery.

Safety and efficiency of modified sacrospinous ligament fixation for apical prolapse: Long-term studies and outcomes.

OBJECTIVE: To explore the safety and efficiency of modified sacrospinous ligament fixation (MSSF) for apical prolapse. METHODS: A retrospective cohort study. Patients diagnosed with apical prolapse from 2014 to 2019 were recruited and divided into three groups: sacrospinous ligament fixation (SSF), MSSF, and laparoscopic sacral hysteropexy (LSH). All surgical characteristics were obtained and information concerning complications was collected and compared among these three groups. RESULTS: A total of 710 patients were included: 108 in the SSF group, 260 in the LSH group, and 342 in the MSSF group. The MSSF and SSF groups took less surgical time (P < 0.001) and had shorter hospital stays (P < 0.001). All three methods can significantly change prolapses to point C on the POP quantification score (P < 0.001). Prevalence of vaginal and pelvic pain after surgery was higher in the SSF group (8/108; 7.41%) (P = 0.028), and urinary incontinence was higher in the LSH group (22/260; 8.46%) (P = 0.010). In the LSH group more patients experienced constipation and dyschezia after surgery (prevalence 18/260; 6.92%; P = 0.048). Recurrence of pelvic organ prolapse in the MSSF group (15/324; 4.39%) and LSH group (12/260; 4.62%) was much lower than in the SSF group (16/108; 14.81%) (P < 0.001). CONCLUSION: The efficacy of MSSF is commendable with low recurrence of POP and few complications in long-term follow up.

Aptamer-based biosensors for the diagnosis of sepsis.

Sepsis, the syndrome of infection complicated by acute organ dysfunction, is a serious and growing global problem, which not only leads to enormous economic losses but also becomes one of the leading causes of mortality in the intensive care unit. The detection of sepsis-related pathogens and biomarkers in the early stage plays a critical role in selecting appropriate antibiotics or other drugs, thereby preventing the emergence of dangerous phases and saving human lives. There are numerous demerits in conventional detection strategies, such as high cost, low efficiency, as well as lacking of sensitivity and selectivity. Recently, the aptamer-based biosensor is an emerging strategy for reasonable sepsis diagnosis because of its accessibility, rapidity, and stability. In this review, we first introduce the screening of suitable aptamer. Further, recent advances of aptamer-based biosensors in the detection of bacteria and biomarkers for the diagnosis of sepsis are summarized. Finally, the review proposes a brief forecast of challenges and future directions with highly promising aptamer-based biosensors.

Fucoidan as a marine-origin prebiotic modulates the growth and antibacterial ability of Lactobacillus rhamnosus.

Fucoidan has received much attention in healthy food and biomedicine owing to their unique (bio)physicochemical properties, particularly antibacterial and antiviral. Pathogenic microorganisms and probiotics are coexisting in many tissues (e.g., gut, oral, and vagina). However, the effect of fucoidan on probiotics has not been examined. Herein, fucoidan sterilized by different methods (i.e., 0.22 µm filter and high-temperature autoclave) is applied to explore its effect on the responses of Lactobacillus rhamnosus. It is found that high-temperature autoclave treatment causes the depolymerization of fucoidan. Further, the proliferation, morphology, and metabolism of probiotics are greatly dependent on the concentrations of fucoidan. The formation of probiotic biofilm is reduced with an increased concentration of fucoidan. Moreover, the antibacterial ability of probiotics initially increases and then decreases with an increased concentration of fucoidan. Thus, fucoidan could serve as a new marine-origin prebiotic, offering new insight into probiotic modulation and its application in inhibiting bacterial infections.