Comparison of the 3-D mesh and Sugarbaker repair for parastomal hernia: a single center experience in China.

Parastomal hernias (PSH) are difficult to manage and associated with high rates of postoperative recurrence and complications. Sugarbaker and three-dimensional (3-D) mesh repair are commonly used methods for the surgical treatment of PSH. However, the efficacy and safety of these surgical techniques have not been adequately compared. Patients with PSH who received 3-D mesh or Sugarbaker repair at our center from August 2012 to May 2023 were included. We retrospectively analyzed their demographic data and postoperative outcomes. The primary outcome measure was the recurrence rate at 1-year follow-up. A total of 86 patients were enrolled, involving 53 in the 3-D mesh (62%) group and 33 in the Sugarbaker (38%) group. Most cases (73%) involved were the laparoscopic approach. The recurrence rate at 1-year follow-up was 15% (eight cases) in the 3-D mesh group and 24% (eight cases) in the Sugarbaker group, with no statistical significance (P = 0.29). Additionally, no differences were observed between the 3-D mesh and Sugarbaker groups in the length of hospitalization or in short- and long-term complications. Sugarbaker and 3-D mesh repair have similar clinical efficacy in the surgical treatment of PSH. Further randomized controlled trials are required to confirm these results.Trial registration number.This study was retrospectively registered at clinicaltrials.gov (NCT06077318).

PSTPIP2 protects against alcoholic liver injury and invokes STAT3-mediated suppression of apoptosis.

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.

Low-valent-tungsten catalysis enables hydroboration of esters and nitriles.

In the research presented herein, low-valent-tungsten-catalyzed hydroboration of esters and nitriles was investigated. Aromatic and aliphatic substrates were smoothly reduced to corresponding alcohol derivatives and N,N-diborylamines in the presence of W(CO)4(NCMe)2. Valuable derivatives were conveniently accessed by introducing a further functionalization process to crude hydroboration mixtures in one pot.

Suture repair versus mesh repair in elderly populations with incarcerated or strangulated groin hernia.

Tension-free hernia repair is the gold standard for groin hernia repair. However, the optimal surgical treatment for incarcerated or strangulated groin hernia in elderly populations is controversial. The aim of this study is to compare the clinical efficacy of mesh repair and suture repair in the treatment of incarcerated or strangulated groin hernia in elderly patients. Patients ≥ 65 years who underwent urgent surgical repair for incarcerated or strangulated groin hernia from January 2012 to June 2022 were included. Patients' demographic data and postoperative outcomes were retrospectively analyzed. Patients with limited life expectancy were screened from the elderly population for subgroup analysis. A total of 103 patients (median age: 84 years old, range 65-96; mean follow-up time: 36.8 ± 24.8 months) were included, involving 42 cases in the suture repair group and 61 cases in the mesh repair group. Suture repair and mesh repair had similar lengths of ICU and hospital stay, and rates of small bowel resection, chronic pain, surgical site infection, and surgical-related death. However, suture repair had a significantly higher recurrence rate than mesh repair (7% vs. 2%, P = 0.04). In our subgroup analysis, for patients with limited life expectancy (41 patients; median age: 88 years old, range: 80-96), suture repair had no statistical difference in postoperative outcomes compared with mesh repair. Mesh repair is suitable for elderly patients with acutely incarcerated or strangulated groin hernias. However, for elderly patients with limited life expectancy, suture repair and mesh repair showed similar clinical outcomes.

Mussel inspired sequential protein delivery based on self-healing injectable nanocomposite hydrogel.

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.

Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity.

Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.

Zwitterionic Aqua Palladacycles with Noncovalent Interactions for meta-Selective Suzuki Coupling of 3,4-Dichlorophenol and 3,4-Dichlorobenzyl Alcohol in Water.

The site-selective reaction of substrates with multiple reactive sites has been a focus of the current synthetic chemistry. The use of attractive noncovalent interactions between the catalyst and substrate is emerging as a versatile approach to address site-selectivity challenges. Herein, we designed and synthesized a series of palladacycles, to control meta-selective Suzuki coupling of 3,4-dichlorophenol and 3,4-dichlorobenzyl alcohol. Noncovalent interactions directed zwitterionic aqua palladacycles catalyzed meta-selective Suzuki couplings of 3,4-dichloroarenes bearing hydroxyl in water have been developed. Experiments and density functional theory (DFT) calculations demonstrated that the electrostatic interactions play a critical role in meta-selective coupling of 3,4-dichlorophenol, while meta-selective coupling of 3,4-dichlorobenzyl alcohol arises due to the hydrogen-bonding interactions.

Enhancing reductive C-N coupling of nitrocompounds through interfacial engineering of MoO2 in thin carbon layers.

In this study, we developed an approach by coating silica nanospheres with polydopamine and metal precursor, followed by carbonization to create interfacial engineered MoO2. The presence of numerous crystal interfaces and metal-carbon interactions resulted in a remarkable enhancement of C-N coupling activity and stability of catalyst compared to one obtained by air calcination.

Routine gastric suspension technique in single-port sleeve gastrectomy procedure.

BACKGROUND: Due to limited technical demand, single-port sleeve gastrectomy (SPSG) is a feasible laparoscopic technique for sleeve gastrectomy (SG). Nonetheless, difficulties exist when performing the single-port technique, and in this study, we aim to describe a slight maneuver that can improve the SPSG procedure. METHODS: Patients who underwent laparoscopic SG between January 2022 and May 2023 at our hospital were included. The patients were classified into two groups: (1) SPSG and (2) multiple-port SG (MPSG). The parameters for this analysis were the patients' age, gender, weight, body mass index (BMI), conversion rate, drainage placement, 30-day readmission rate, and postoperative complications. Postoperative one-month and three-month percentages of total weight loss (%TWL) were calculated and compared. RESULTS: 171 patients were included in this study: (1) the SPSG group (n = 96) and (2) the MPSG group (n = 75). No statistically significant difference was observed within the preoperative (age, gender, height, weight, and BMI) and the perioperative parameters between SPSG and MPSG (operation time, drainage placement, 30-day readmission) (p > 0.05). Per Clavien-Dindo's grading, two patients in the SPSG group suffered grade 1 complications; for the MPSG group, one patient sustained grade 2 and another suffered grade 3b complication. No statistical significance was observed on the %TWL between the two groups (p > 0.05). CONCLUSION: Our study found that performing SPSG in specific patient is feasible and non-inferior when compared to the MPSG. Further studies will be needed to elucidate better the efficacy and safety of performing SPSG.

High efficiency removal of organic and inorganic iodine with ferrate[Fe(VI)] through oxidation and adsorption.

I- is a halogen species existing in natural waters, and the transformation of organic and inorganic iodine in natural and artificial processes would impact the quality of drinking water. Herein, it was found that Fe(VI) could oxidize organic and inorganic iodine to IO3-and simultaneously remove the resulted IO3- through Fe(III) particles. For the river water, wastewater treatment plant (WWTP) effluent, and shale gas wastewater treated by 5 mg/L of Fe(VI) (as Fe), around 63 %, 55 % and 71 % of total iodine (total-I) had been removed within 10 min, respectively. Fe(VI) was superior to coagulants in removing organic and inorganic iodine from the source water. Adsorption kinetic analysis suggested that the equilibrium adsorption amount of I- and IO3- were 11 and 10.1 µg/mg, respectively, and the maximum adsorption capacity of IO3- by Fe(VI) resulted Fe(III) particles was as high as 514.7 µg/mg. The heterogeneous transformation of Fe(VI) into Fe(III) effectively improved the interaction probability of IO3- with iron species. Density functional theory (DFT) calculation suggested that the IO3- was mainly adsorbed in the cavity (between the γ-FeOOH shell and γ-Fe2O3 core) of Fe(III) particles through electrostatic adsorption, van der Waals force and hydrogen bond. Fe(VI) treatment is effective for inhibiting the formation of iodinated disinfection by-products in chlor(am)inated source water.

Classification of subtypes and identification of dysregulated genes in sepsis.

Background: Sepsis is a clinical syndrome with high mortality. Subtype identification in sepsis is meaningful for improving the diagnosis and treatment of patients. The purpose of this research was to identify subtypes of sepsis using RNA-seq datasets and further explore key genes that were deregulated during the development of sepsis. Methods: The datasets GSE95233 and GSE13904 were obtained from the Gene Expression Omnibus database. Differential analysis of the gene expression matrix was performed between sepsis patients and healthy controls. Intersection analysis of differentially expressed genes was applied to identify common differentially expressed genes for enrichment analysis and gene set variation analysis. Obvious differential pathways between sepsis patients and healthy controls were identified, as were developmental stages during sepsis. Then, key dysregulated genes were revealed by short time-series analysis and the least absolute shrinkage and selection operator model. In addition, the MCPcounter package was used to assess infiltrating immunocytes. Finally, the dysregulated genes identified were verified using 69 clinical samples. Results: A total of 898 common differentially expressed genes were obtained, which were chiefly related to increased metabolic responses and decreased immune responses. The two differential pathways (angiogenesis and myc targets v2) were screened on the basis of gene set variation analysis scores. Four subgroups were identified according to median expression of angiogenesis and myc target v2 genes: normal, myc target v2, mixed-quiescent, and angiogenesis. The genes CHPT1, CPEB4, DNAJC3, MAFG, NARF, SNX3, S100A9, S100A12, and METTL9 were recognized as being progressively dysregulated in sepsis. Furthermore, most types of immune cells showed low infiltration in sepsis patients and had a significant correlation with the key genes. Importantly, all nine key genes were highly expressed in sepsis patients. Conclusion: This study revealed novel insight into sepsis subtypes and identified nine dysregulated genes associated with immune status in the development of sepsis. This study provides potential molecular targets for the diagnosis and treatment of sepsis.

Calcium dobesilate prevents PLD-induced hand-foot syndrome by alleviating capillary endothelial tight junction injury via the HA/CD44 pathway.

Pegylated liposomal doxorubicin (PLD) has excellent therapeutic efficacy in the treatment of cancers, but can cause serious adverse reactions such as hand-foot syndrome (HFS). Our previous research suggests that both PLD-induced HFS may be associated with injury to tight junctions (TJs) in the skin and that calcium dobesilate (CaD) can alleviate HFS. However, the underlying molecular mechanism is not well understood. Here, we created an in vitro PLD-treated model using Human Microvascular Endothelial Cell line-1 (HMEC-1) and an in vivo HFS rat model to investigate the underlying pathways. Treatment with PLD increased the expression of HYAL-1, CD44, and hyaluronic acid (HA) concentration, while reducing ZO-1 and Claudin-5 expression. Moreover, PLD treatment induced the degradation of higher molecular weight HA to its lower molecular weight counterpart, elevating the permeability of both HEMC-1 cell membranes and rat paw skin capillaries. AD-01 (CD44 inhibitor) inhibited the effect of PLD on the expression of ZO-1 and Claudin-5. Furthermore, CaD treatment suppressed the expression of HYAL-1 and CD44, mitigated HA degradation, and enhanced the expression of ZO-1 and Claudin-5. This resulted in decreased permeability in HEMC-1 cells and rat skin capillaries. In summary, our data suggest that PLD may promote the destruction of TJs via the HA/CD44 pathway, thereby leading to HFS through increased skin permeability and exacerbated doxorubicin extravasation. Moreover, CaD can inhibit this pathway, offering a potential therapeutic avenue to alleviate HFS.

Correspondence on "Structural Insight into the Catalytic Mechanism of the Endoperoxide Synthase FtmOx1".

In their recent Angewandte Chemie publication (doi: 10.1002/anie.202112063), Cen, Wang, Zhou et al. reported the crystal structure of a ternary complex of the non-heme iron endoperoxidase FtmOx1 (PDB entry 7ETK). The biochemical data assessed in this study were from a retracted study (doi: 10.1038/nature15519) by Zhang, Liu, Zhang et al.; no additional biochemical data were included, yet there was no discussion on the source of the biochemical data in the report by Cen, Wang, Zhou et al. Based on this new crystal structure and subsequent QM/MM-MD calculations, Cen, Wang, Zhou et al. concluded that their work provided evidence supporting the CarC-like mechanistic model for FtmOx1 catalysis. However, the authors did not accurately describe either the CarC-like model or the COX-like model, and they did not address the differences between them. Further, and contrary to their interpretations in the manuscript, the authors' data are consistent with the COX-like model once the details of the CarC-like and COX-like models have been carefully analyzed.

New small-molecule alcohol synthesis by breaking the space limitation of the "aromatic cage" in Pseudomonas sp. AK1 BBOX.

Fe(II)/2OG-dependent oxygenase γ-butyrobetaine hydroxylase (BBOX) stereoselectively hydroxylates inactive C-H bonds and produces L-carnitine. It has potential applications in the biosynthesis of L-carnitine and the synthesis of other small molecule alcohols. In this paper, we systematically explore the substrate range of Pseudomonas sp. AK1 BBOX (psBBOX), with emphasis on the quaternary ammonium portion of γ-butyrobetaine (γ-BB). The space limitation of the "aromatic cage" in psBBOX in the hydroxylation of large quaternary ammonium analogues was studied, and the role of four aromatic amino acid residues in the substrate binding mode was analyzed. Consequently, the F188A mutant was developed with the ability to hydroxylate cyclic quaternary ammonium analogues and generate new alcohol compounds by breaking the limitation of the "aromatic cage".

Fault diagnosis for wind turbines with graph neural network model based on one-shot learning.

Because of the harsh working environment, there is usually a lack of effective data from the gearboxes of wind turbines for fault classification. In this paper, a fault-diagnosis model based on graph neural networks and one-shot learning is proposed to solve the problem of fault classification with limited data. In the proposed method, the short-time Fourier transform is used to convert one-dimensional vibration signals into two-dimensional data, then feature vectors are extracted from the two-dimensional data, and small-sample learning is achieved. An experimental rig was built to simulate the real working scenario of a wind turbine, and the results indicate the high classification accuracy of the proposed method. Furthermore, its effectiveness is verified in comparisons with Siamese, matching and prototypical networks, with the proposed method outperforming all of them.

Synthetic Versus Biological Mesh in Ventral Hernia Repair and Abdominal Wall Reconstruction: A Systematic Review and Recommendations from Evidence-Based Medicine.

AIM: To compare the efficacy and safety of synthetic and biological meshes in ventral hernia repair (VHR) and abdominal wall reconstruction (AWR). METHODS: We screened all clinical trials that reported the application of synthetic and biological meshes in VHR and AWR using Medline, Web of Science, and Embase (Ovid). Only comparative studies with similar baselines such as age, sex, body mass index, degree of wound contamination, and hernia defects between the intervention and control groups were included. Effect sizes with 95% confidence were pooled using a random- or fixed-effects model based on the size of heterogeneity. A sensitivity analysis was performed to test the stability of the results. RESULTS: Ten studies with 1305 participants were included. Biological meshes were associated with significantly higher recurrence rate (OR, 2.09; 95% CI 1.42-3.08; I2 = 50%), surgical site infection (OR, 1.47; 95% CI 1.10-1.97; I2 = 30%), higher re-admission rate (OR, 1.51; 95% CI 1.05-2.17; I2 = 50%), and longer length of hospital stay (SMD, 0.37; 95% CI 0.10-0.65; I2 = 72%). Similar surgical site occurrence, re-operation rate, and mesh explantation rate were observed among biological and synthetic meshes. Biological meshes have no difference in recurrence rate as compared to synthetic meshes, between the clean-contaminated, and contamination-infected fields (OR, 1.41; 95% CI 0.41-4.87 vs 3.00; 95% CI 1.07-8.46; P = 0.36). CONCLUSION: Synthetic meshes are a safe alternative to biological meshes for VHR and AWR. Considering the high cost of biological meshes, synthetic meshes are more appropriate for the VHR and AWR.

Rhodium-Catalyzed Enantioselective 1,4-Oxyamination of Conjugated gem-Difluorodienes via Coupling with Carboxylic Acids and Dioxazolones.

The incorporation of fluorine atoms in organics improves their bioactivity and lipophilicity. Catalytic functionalization of gem-difluorodienes represents one of the most straightforward approaches to access fluorinated alkenes. In contrast to the regular 1,3-dienes that undergo diverse asymmetric di/hydrofunctionalizations, the regio- and enantioselective oxyamination of gem-difluorodienes remains untouched. Herein, we report asymmetric 1,4-oxyamination of gem-difluorodiene by chiral rhodium-catalyzed three-component coupling with readily available carboxylic acid and dioxazolone, affording gem-difluorinated 1,4-amino alcohol derivatives. Our asymmetric protocol exhibits high 1,4-regio- and enantioselectivity with utility in the late-stage modification of pharmaceuticals and natural products. Stoichiometric experiments provide evidences for the π-allylrhodium pathway. Related oxyamination was also realized when trifluoroethanol was used as an oxygen nucleophile.

Microneedle Patches with Antimicrobial and Immunomodulating Properties for Infected Wound Healing.

Treatment of infected wounds remains a challenge owing to antibiotic resistance; thus, developing smart biomaterials for the healing of infected wounds is urgently needed. In this study, a microneedle (MN) patch system with antimicrobial and immunomodulatory properties is developed to promote and accelerate infected wound healing. In the MN patch (termed PFG/M MNs), a nanoparticle with polydopamine (PDA)-loaded iron oxide is grafted with glucose oxidase (GOx) and hyaluronic acid (HA) and then integrated into the tips, and amine-modified mesoporous silica nanoparticles (AP-MSNs) are incorporated into the bases. Results show that PFG/M MNs eradicate bacterial infections and modulate the immune microenvironment, combining the advantages of chemodynamic therapy, photothermal therapy, and M2 macrophage polarization from Fe/PDA@GOx@HA in the tips as well as anti-inflammatory effect of AP-MSNs from the MN bases. Thus, the PFG/M MN system is a promising clinical candidate for promoting infected wound healing.

Asymmetric Synthesis of Spiropyrazolone-Fused Dihydrofuran-naphthoquinones Bearing Contiguous Stereocenters via a Michael Addition/Chlorination/Nucleophilic Substitution Sequence.

An enantioselective synthesis of spiropyrazolone-fused dihydrofuran-naphthoquinones is first demonstrated via a Michael addition/Chlorination/Nucleophilic substitution sequence. The reactions of 2-hydroxy-1,4-naphthoquinone and α,ß-unsaturated pyrazolones in the presence of the cinchona alkaloid derived hydrogen-bonding catalyst and NCS provide spiropyrazolone-fused 2,3-dihydronaphtho[2,3-b]furan-4,9-diones bearing contiguous stereocenters, of which one is the spiro quaternary stereocenter in high yields with exclusive diastereoselectivity and good to excellent enantioselectivities.

Mitochondria-targeting NIR AIEgens with cationic amphiphilic character for imaging and efficient photodynamic therapy.

A new dual-cationic amphiphilic AIEgen TPhBT-PyP with NIR emission and efficient 1O2 generation was designed. The amphiphilicity of TPhBT-PyP was tuned with dual-positive charges of pyridinium and TPP groups, efficiently targeting mitochondria and distinguishing Gram-positive bacteria. TPhBT-PyP performed well in photodynamic therapy, inducing cancer cell apoptosis and killing S. aureus bacteria.