A novel technique for the single-port laparoscopic percutaneous extraperitoneal closure (SLPEC) of paediatric isolated giant inguinal hernias using double-modified hernia needles.

The objective was to explore the efficacy of single-port laparoscopic percutaneous extraperitoneal closure using double-modified hernia needles with hydrodissection (SLPEC group) and two-port laparoscopic percutaneous extraperitoneal closure (TLPEC group) for the treatment of giant indirect inguinal hernias in children. We performed a retrospective review of all children with giant indirect inguinal hernias (inner ring orifice diameter ≥ 1.5 cm) who underwent laparoscopic high ligation of the hernia sac at FuJian Children's Hospital from January 2019 to December 2021. We collected data from the medical records of all the children and analysed their clinical characteristics and operation-related and follow-up information. Overall, this study included a cohort of 219 patients with isolated giant inguinal hernias who had complete clinical data and who had undergone laparoscopic high ligation of the hernia sac at our centre. All procedures were successfully performed for the 106 patients who underwent SLPEC and for the 113 patients who underwent TLPEC at our centre. There were no statistically significant differences in patient age, sex, body weight, follow-up time or the side of inguinal hernia between the SLPEC group and the TLPEC group (P = 0.123, 0.613, 0.121, 0.076 and 0.081, respectively). However, there were significant differences in the bleeding volume, visual analogue scale (VAS) score, and postoperative activity time between the two groups (P ≤ 0.001). The operation times in the TLPEC group were significantly longer than those in the SLPEC group (P = 0.048), but there were no significant differences in hospital length of stay or hospitalization costs between the two groups (P = 0.244 and 0.073, respectively). Incision scars were found in 2 patients in the SLPEC group and 9 patients in the TLPEC group, and there was a significant difference between the two groups (P = 0.04). However, the incidence of ipsilateral hernia recurrence, surgical site infection, suture-knot reactions and chronic inguinodynia did not significantly differ between the two groups (P = 0.332, 0.301, 0.332 and 0.599, respectively). Postoperative hydrocele occurred in only 1 male child in the SLPEC group and in no male children in the TLPEC group, and there was no difference between the two groups (P = 0.310). In this study, there were no cases of testicular atrophy or iatrogenic ascent of the testis. Compared with the TLPEC group, the SLPEC group had the advantages of a concealed incision, light scarring, minimal invasiveness, a reduced operation time, minimal bleeding, mild pain and rapid recovery. In conclusion, SLPEC using double-modified hernia needles with hydrodissection and high ligation of the hernia sac is a safe, effective and minimally invasive surgery. The cosmetic results are impressive, and the follow-up results are promising.

Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection.

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-ß1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1ß) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

GBP1 promotes cutaneous squamous cell carcinoma proliferation and invasion through activation of STAT3 by SP1.

Cutaneous squamous cell carcinoma (cSCC) ranks as the second most prevalent skin tumour (excluding melanoma). However, the molecular mechanisms driving cSCC progression remain elusive. This study aimed to investigate GBP1 expression in cSCC and elucidate its potential molecular mechanisms underlying cSCC development. GBP1 expression was assessed across public databases, cell lines and tissue samples. Various assays, including clone formation, CCK8 and EdU were employed to evaluate cell proliferation, while wound healing and transwell assays determined cell migration and invasion. Subcutaneous tumour assays were conducted to assess in vivo tumour proliferation, and molecular mechanisms were explored through western blotting, immunofluorescence and immunoprecipitation. Results identified GBP1 as an oncogene in cSCC, with elevated expression in both tumour tissues and cells, strongly correlating with tumour stage and grade. In vitro and in vivo investigations revealed that increased GBP1 expression significantly enhanced cSCC cell proliferation, migration and invasion. Mechanistically, GBP1 interaction with SP1 promoted STAT3 activation, contributing to malignant behaviours. In conclusion, the study highlights the crucial role of the GBP1/SP1/STAT3 signalling axis in regulating tumour progression in cSCC. These findings provide valuable insights into the molecular mechanisms of cSCC development and offer potential therapeutic targets for interventions against cSCC.

Digital Sort-Enabled Counting Allows Absolute Electrical Quantification of Target Nucleic Acid.

Quantitative nucleic acid amplification tests are of great importance for diagnostics, but current approaches require complex and costly optical setups that limit their nonlaboratory applications. Herein we describe the implementation of a microfluidics platform that can perform binary DNA-amplification-activated droplet sorting. The digital sort-enabled counting (DISCO) platform enables label-free absolute quantification of the nucleic acid. This is achieved by provoking a pH change in droplets through a loop-mediated isothermal amplification (LAMP) reaction, followed by using sorting by interfacial tension (SIFT) to direct positive and negative droplets to different outlets. With the use of on-chip electrodes at both outlets, we demonstrate that the digital electrical counting of target DNA and RNA can be realized. DISCO is a promising approach for realizing sensitive nucleic acid quantification in point-of-care settings.

A single-cell profile reveals the transcriptional regulation responded for Abelmoschus manihot (L.) treatment in diabetic kidney disease.

BACKGROUND: Huangkui capsule (HKC), as an ethanol extract of Abelmoschus manihot (L.), has a significant efficacy in treatment of the patients with diabetic kidney disease (DKD). The bioactive ingredients of HKC mainly include the flavonoids such as rutin, hyperoside, hibifolin, isoquercetin, myricetin, quercetin and quercetin-3-O-robinobioside. PURPOSE: To explore the molecular mechanisms of A. manihot in treatment of DKD. STUDY DESIGN: A single-cell RNA sequencing analysis of kidneys in db/db mice with and without HKC administration. METHODS: Urinary biochemical and histopathological examination in C57BL/6 and db/db mice of DKD and HKC groups was done. Single-cell RNA sequencing pipeline was then performed. The regulatory mechanisms of seven flavonoids in HKC were revealed by cell communication, prediction of transcription factor regulatory network, and molecular docking. RESULTS: By constructing ligand-receptor regulatory network and performing molecular docking between 75 receptors with different activities and seven flavonoids. 11 key receptors in 4 cell types (segment 3 proximal convoluted tubular cell, ascending limbs of the loop of Henle, distal convoluted tubule, and T cell) in kidneys were found to be directly interacted with HKC. The interactions regulated 8 downstream regulons. The docking receptors in T cell led to transcriptional event differences in the regulons such as Cebpb, Rel, Tbx21 and Klf2 and consequently affected the activation, differentiation, and infiltration of T cell, while the receptors Tgfbr1 and Ldlr in stromal cells of kidneys were closely associated with the downstream transcriptional events of renal injury and proteinuria in DKD. CONCLUSION: The current study provides novel information of the key receptors and regulons in renal cells for a better understanding of the cell type specific molecular mechanisms of A. manihot in treatment of DKD.

Inhibition of Let-7b-5p maturation by LIN28A promotes thermal skin damage repair after burn injury.

Burn injuries, especially severe ones, result in direct and indirect thermal damage to skin tissues, with a complex and slow wound healing process. Improper treatment can induce sustained inflammatory responses, causing systemic damage. Lin28A, a highly conserved RNA binding protein, was found to exert a significant effect on cell proliferation and wound repair. Lin28A exerts the functions through inhibiting the maturation of the let-7 family miRNAs. Herein, the roles of Lin28A and let-7b in thermal injury repair were investigated using a mouse thermal injury model and a human skin fibroblast (HSF) model for thermal injuries. Lin28A could inhibit the maturation of let-7b, thus participating in skin repair after burns. In the animal model, Lin28A was highly expressed after thermal injury. In the HSF model for thermal injuries, downregulation of Lin28A inhibited the proliferation, migration, and extracellular matrix (ECM) generation of fibroblasts. When let-7b was knocked down in HSFs, the impacts on fibroblast functions caused by downregulation of Lin28A were partially reversed. Moreover, let-7b overexpression might significantly attenuate the promotive effects of Lin28A upon thermal injury repair. Finally, AKT2 and IGF1R were the let-7b target genes within cells. These findings reveal that Lin28A might promote thermal injury repair in burn-injured skin by inhibiting the maturation of let-7b and improving HSF viability and functions, thus illustrating the critical effect of let-7b on burn wound healing and providing new therapeutic targets and strategies for burn treatment.

Research on the fiber intensity modulation model of superconducting magnetic levitation rotor.

The measurement of the pole axis deviation angle of superconducting magnetic levitation rotors plays a crucial role in the field of high-precision navigation. This article conducts theoretical analysis and experimental research on the diffuse reflection intensity modulation principle of optical fiber sensors and the ideal diffuse reflection modulation model under ideal conditions. First, the structural distribution of optical fiber sensors is presented, and the principle of measuring the polar deviation angle of superconducting magnetic levitation rotors is analyzed. Then, based on the diffuse reflection intensity modulation principle, an optical fiber intensity modulation model for ideal superconducting magnetic levitation rotors is established. The correctness of this model was verified through simulation and calibration experiments, and the error between the simulation and experimental results was less than 8%.

THOC7-AS1/OCT1/FSTL1 axis promotes EMT and serves as a therapeutic target in cutaneous squamous cell carcinoma.

BACKGROUND: THOC7-AS1 and FSTL1 expression are frequently upregulated in cutaneous squamous cell carcinoma (cSCC). However, their molecular biological mechanisms remain elusive and their potential as therapeutic targets needs urgent exploration. METHODS: Human tissue samples were used to evaluate clinical parameters. In vitro and in vivo experiments assessed biological functions. Quantitative PCR, western blot, immunohistochemistry, immunocytochemistry, immunoprecipitation, RNA fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation, silver staining, chromatin immunoprecipitation, dual luciferase reporter assays etc. were utilized to explore the molecular biological mechanisms. RESULTS: We found FSTL1 is an oncogene in cSCC, with high expression in tumor tissues and cells. Its elevated expression closely associates with tumor size and local tissue infiltration. In vitro and in vivo, high FSTL1 expression promotes cSCC proliferation, migration and invasion, facilitating malignant behaviors. Mechanistically, FSTL1 interacts with ZEB1 to promote epithelial-to-mesenchymal transition (EMT) in cSCC cells. Exploring upstream regulation, we found THOC7-AS1 can interact with OCT1, which binds the FSTL1 promoter region and promotes FSTL1 expression, facilitating cSCC progression. Finally, treating tumors with THOC7-AS1 antisense oligonucleotides inhibited cSCC proliferative and migratory abilities, delaying tumor progression. CONCLUSIONS: The THOC7-AS1/OCT1/FSTL1 axis regulates EMT and promotes tumor progression in cSCC. This study provides clues and ideas for cSCC targeted therapy.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

Three-dimensional donor-acceptor conjugated porous polymers based on metal-porphyrin and triazine for highly effective photodegradation of organic pollutants in water.

Three-dimensional donor-acceptor (D-A) type conjugated porous polymers (CPPs) was designed and synthesized via imine condensation of copper tetraaminoporphyrin (CuTAPP) as donor and 1,3,5-tris-(4-formyl phenyl) triazine (TFPT) as acceptor, named as CuPT-CPP. The CuPT-CPP possesses a high specific surface area (73.7 m2/g) and excellent photophysical properties. The simultaneous introduction of the organometallic molecules and D-A structures in CuPT-CPP could be broadened the visible-light response range (400-800 nm) and facilitated efficient photogenerated carrier separation and transportation. As heterogeneous photocatalysts, CuPT-CPP has excellent photocatalytic performances under visible light irradiation, leading to excellent model pollutant rhodamine B degradation efficiency up to about 100% in 3 h, it has superb stability and reusability during the photocatalytic processes, and CuPT-CPP also exhibited broad substrate adaptability, which could photocatalytic degradation of methylene blue (MB), methyl orange (MO), and tetracycline hydrochloride (TC). This work indicates that three-dimensional D-A type porphyrin- and triazine-based CuPT-CPP has great potential in the practical application of photocatalysis.

Numerical Simulation on Erosion and Stress on a Small-Diameter Hydrajet Fracturing Tool.

Conventional hydrajet fracturing techniques are often frustrated when they are applied to some specific well types, such as casing-damaged and small-diameter wells. It is of great significance to investigate the erosion and stress on a small-diameter hydrajet fracturing tool during its service and clarify the relevant influencing factors. Based on the solid-liquid two-phase flow theory and erosion model, a numerical simulation was conducted on the erosion and stress on a small-diameter hydrajet fracturing tool by using the computational fluid dynamics approach in order to understand how the inlet flow rate, particle size, and particle mass concentration affect the erosion and stress on the tool. The results show that the erosion on the small-diameter hydrajet fracturing tool is generally a cutting erosion of proppant particles on the tool body. Such erosion occurs on the lower wall of the nozzle, and the erosion at the upper-0° nozzle is higher in rate and smaller in area than that at the lower-180° nozzle. The maximum stress of the small-diameter hydrajet fracturing tool is concentrated on the upper and lower walls of the upper and lower nozzles, especially the lower part inside the upper nozzle. The maximum erosion rate, average erosion rate, and maximum stress on the wall near the nozzle during fracturing increase as the inlet flow rate and particle mass concentration increase and decrease as the proppant particle size increases.

Recent progress in functional metal-organic frameworks for bio-medical application.

Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Evaluating testicular function changes in unilateral cryptorchid chinese infants underwent orchidopexy in the first year of life.

OBJECTIVE: Management of cryptorchidism is typically recommended within the first 18 months of life to maximize fertility potential. However, there is a paucity of longitudinal postoperative data for Chinese infants. We aim to evaluate the Testicular function change when the procedure is done within the first year of life. METHOD: We prospectively enrolled 51 children diagnosed with unilateral inguinal cryptorchidism into the surgical group between January 2021 and January 2022. Orchidopexy was carried out through a single transverse scrotal incision. Assessments of anti-Mullerian hormone (AMH), inhibin B (InhB), testosterone (T) levels, testicular volume and testicular atrophy index (TAI) were conducted at baseline, 6 months, and 1 year following surgery. Concurrently, clinical data from 42 healthy age-matched controls were collected during their routine physical examinations. RESULTS: At 6- and 12-months post-surgery, testicular volume increased significantly to 0.98 ± 0.12 mL and 1.01 ± 0.12ml. AMH levels also rose from 76.40 ± 15.77 ng/mL to 81.52 ± 15.32 ng/mL and 87.50 ± 15.36 ng/mL. However, these parameters are significantly lower than age-matched healthy controls (both P < 0.001). InhB levels significantly increased after surgery and even surpassed those of healthy controls after 6 months (both P < 0.001). The TAI was 16.7% and 8.6% at 6- and 12-months following surgery. CONCLUSION: Although orchiopexy can improve testicular growth and function, the restoration of testicular function to the level of healthy peers might take longer. To expedite the recovery of testicular function and bring it in line with that of peers, we recommend addressing cryptorchidism at the earliest opportunity.

Double J stent combined with pyelostomy tube in pediatric laparoscopic pyeloplasty: a 5-year clinical experience in a single center.

OBJECTIVE: To compare the outcome of using a double J (DJ) stent combined with pyelostomy tube with a DJ stent alone in laparoscopic pyeloplasty (LP) for pediatric ureteropelvic junction obstruction (UPJO). METHODS: A retrospective review of all patients with UPJO treated with LP between January 2017 and November 2021 was conducted in our center. According to different postoperative drainage methods patients were divided into a DJ stent group (52 cases) and a DJ stent combined with pyelostomy tube group (combination group, 41 cases). Operative time, bleeding volume, perirenal drainage stent removal time, postoperative hospital stay, postoperative complications, and renal function recovery were compared between the two groups. Renal ultrasound and diuretic renogram (DR) were used for preoperative and postoperative follow-up. RESULTS: A total of 52 patients were in the DJ stent group and 41 patients in the combination group. The mean hospital stay was 6.46 ± 2.66 days in the DJ stent group and 5.22 ± 1.63 days in the combination group (p < 0.05). Postoperative complications developed in 14 out of 52 patients in the DJ stent group (26.9%), while complications developed in 8 out of 41 patients in the combination group (19.5%) (p > 0.05). Non-catheter-related complications developed in 10/52 patients in the DJ stent group (19.2%) and only 1/41 patients in the combination group (2.4%) (p < 0.05). The renal function and renal cortex thickness in both groups were improved. CONCLUSION: Both the DJ stent drainage and the DJ stent combined with pyelostomy drainage are safe and effective. We should fully consider the patient's preoperative and intraoperative conditions and choose appropriate drainage methods. A DJ stent combined with pyelostomy tube can reduce non-catheter related complications, facilitate postoperative recovery, and the hospital stay was significantly shorter than the DJ stent group. However, it is necessary to pay attention to the nursing treatment of the pyelostomy tube and guard against the occurrence of pyelostomy tube shedding.

Sources and hydrogeochemical processes of groundwater under multiple water source recharge condition.

Ecological water replenishment (EWR) is an essential approach for improving the quantity and quality of regional water. The Chaobai River is a major river in Beijing that is replenished with water from multiple sources, including reclaimed water (RW), the South-North Water Transfer Project (SNTP), reservoir discharge (RD). The effects of multiple water source recharge (MWSR) on groundwater quality remain unclear. In this study, hydrochemical ions, isotopes (δ2H-H2O, δ18O-H2O, δ15N-NO3-, and δ18O-NO3-), mixing stable isotope analysis in R (MixSIAR), and hydrogeochemical modeling were used to quantify the contributions and impacts of different water sources on groundwater and to propose a conceptual model. The results showed that during the period before reservoir discharge, RW and SNTP accounted for 38 %-41 % and 54 % of the groundwater in their corresponding recharge areas, respectively. The groundwater in the RW recharge area contained high levels of Na+ and Cl- leading to the precipitation of halite, and was the main factor for the spatial variation in groundwater hydrochemical components. The surface water changed from Na·K - Cl·SO4 type to Ca·Mg - HCO3 type which was similar to groundwater after reservoir discharge. RD accounted for 30 % of the groundwater; however, it did not change the hydrochemical type of groundwater. Dual nitrate stable isotopes and MixSIAR demonstrated that RW was the primary source of NO3- in groundwater, contributing up to 76-89 %, and reservoir discharge effectively reduced the contribution of RW. δ15N-NO3- or δ18O-NO3- in relation to NO3-N suggests that denitrification is the main biogeochemical process of nitrogen in groundwater, whereas water recharge from the SNTP and RD reduces denitrification and dilutes NO3-. This study provides insights into the impact of anthropogenically controlled ecological water replenishment from different water sources on groundwater and guides the reasonable allocation of water resources.

Single-Cell Transcriptional Landscape Reveals the Regulatory Network and Its Heterogeneity of Renal Mitochondrial Damages in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is one of the common chronic microvascular complications of diabetes in which mitochondrial disorder plays an important role in its pathogenesis. The current study delved into the single-cell level transcriptome heterogeneity of mitochondrial homeostasis in db/db mice, an animal model for study of type 2 diabetes and DKD, with single-cell RNA sequencing (scRNA-Seq) and bulk RNA-seq analyses. From the comprehensive dataset comprising 13 meticulously captured and authenticated renal cell types, an unsupervised cluster analysis of mitochondria-related genes within the descending loop of Henle, collecting duct principal cell, endothelial, B cells and macrophage, showed that they had two types of cell subsets, i.e., health-dominant and DKD-dominant clusters. Pseudotime analysis, cell communication and transcription factors forecast resulted in identification of the hub differentially expressed genes between these two clusters and unveiled that the hierarchical regulatory network of receptor-TF-target genes was triggered by mitochondrial degeneration. Furthermore, the collecting duct principal cells were found to be regulated by the decline of Fzd7, which contributed to the impaired cellular proliferation and development, apoptosis and inactive cell cycle, as well as diminished capacity for material transport. Thereby, both scRNA-Seq and bulk RNA-Seq data from the current study elucidate the heterogeneity of mitochondrial disorders among distinct cell types, particularly in the collecting duct principal cells and B cells during the DKD progression and drug administration, which provide novel insights for better understanding the pathogenesis of DKD.

Hypoxic Microenvironment Reconstruction with Synergistic Biofunctional Ions Promotes Diabetic Wound Healing.

Chronic hypoxia and ischemia make diabetic wounds non-healing. Cellular functions of diabetic chronic wounds are inhibited under a pathological environment. Therefore, this work develops a composite hydrogel system to promote diabetic wound healing. The composite hydrogel system consists of ε-poly-lysine (EPL), calcium peroxide (CP), and borosilicate glass (BG). The hydrogel supplies continuous dissolved oxygen molecules to the wound that can penetrate the skin tissue to restore normal cellular function and promote vascular regeneration. Biofunctional ions released from BGs can recruit more macrophages through neovascularization and modulate macrophage phenotypic transformation. Combining oxygen-mediated vascular regeneration and ion-mediated inflammatory regulation significantly accelerated diabetic wound healing. These findings indicate that this composite hydrogel system holds promise as a novel tissue engineering material.

Binding-induced fibrillogenesis peptide inhibits RANKL-mediated osteoclast activation against osteoporosis.

Osteoporosis is primarily driven by an imbalance between bone resorption and formation, stemming from enhanced osteoclast activity during bone remodeling. At the crux of this mechanism lies the pivotal RANK-RANKL-OPG axis. In our study, we designed two binding-induced fibrillogenesis (BIF) peptides, namely BIFP and BIFY, targeting RANK and RANKL, respectively. These BIF peptides, with distinct hydrophilic and hydrophobic characteristics, assemble into nanoparticles (NPs) in aqueous solution. Through specific ligand-receptor interactions, these NPs efficiently target and bind to specific proteins, resulting in the formation of fibrous networks that effectively inhibit the RANK-RANKL associations. Experiments have confirmed the potent inhibitory effects of peptides on both osteoclast differentiation and function. Compared with the +RANKL controls, BIFP and BIFY demonstrated a more remarkable reduction in tartrate resistant acid phosphatase (TRAP)-positive cells, achieving an impressive decline of 82.8% and 70.7%, respectively. Remarkably, the administration of BIFP led to a substantial reduction in bone resorption pit area by 17.4%, compared to a significant increase of 92.4% in the +RANKL groups. In vivo experiments on an ovariectomized mouse model demonstrated that the BIFP treated group exhibited an impressive 2.6-fold elevation in bone mineral density and an astounding 4.0-fold enhancement in bone volume/total volume as against those of the PBS-treated group. Overall, BIF peptides demonstrate remarkable abilities to impede osteoclast differentiation, presenting promising prospects for the treatment of osteoporosis.

Improved long-term outcomes after innovative preoperative evaluation and conception of precise surgery for gallbladder cancer.

BACKGROUND: Three-dimensional visualization preoperative evaluation (3D-VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D-VPE and ERAS would improve the outcome of patients undergoing surgery for GBC. OBJECTIVE: This study aimed to determine if 3D-VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC. METHODS: A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D-VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups. RESULTS: Patients who underwent 3D-VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p < 0.001) and dissected lymph node number (26.6 ± 12.6 vs. 16.3 ± 7.6 p < 0.001) compared to the control group. The median survival was 27.4 months, and the 1- and 3-year survival rates were 84.4% and 29.8%, respectively, in patients who received combined management; in the control cohort, the median survival was 12.7 months, and the 1- and 3-year survival rates were 53.5% and 15.1%, respectively. In addition, some postoperative complications and risk factors were diminished relative to the traditionally treated patients. CONCLUSION: The implementation of 3D-VPE and ERAS can significantly improve the prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice.