Clinical application of digital technology in the use of anterolateral thigh lobulated perforator flaps to repair complex soft tissue defects of the limbs.

Background: It is challenging to repair wide or irregular defects with traditional skin flaps, and anterolateral thigh (ALT) lobulated perforator flaps are an ideal choice for such defects. However, there are many variations in perforators, so good preoperative planning is very important. This study attempted to explore the feasibility and clinical effect of digital technology in the use of ALT lobulated perforator flaps for repairing complex soft tissue defects in limbs. Methods: Computed tomography angiography (CTA) was performed on 28 patients with complex soft tissue defects of the limbs, and the CTA data were imported into Mimics 20.0 software in DICOM format. According to the perforation condition of the lateral circumflex femoral artery and the size of the limb defect, one thigh that had two or more perforators from the same source vessel was selected for 3D reconstruction of the ALT lobulated perforator flap model. Mimics 20.0 software was used to visualize the vascular anatomy, virtual design and harvest of the flap before surgery. The intraoperative design and excision of the ALT lobulated perforator flap were guided by the preoperative digital design, and the actual anatomical observations and measurements were recorded. Results: Digital reconstruction was successfully performed in all patients before surgery; this reconstruction dynamically displayed the anatomical structure of the flap vasculature and accurately guided the design and harvest of the flap during surgery. The parameters of the harvested flaps were consistent with the preoperative parameters. Postoperative complications occurred in 7 patients, but all flaps survived uneventfully. All of the donor sites were closed directly. All patients were followed up for 13-27 months (mean, 19.75 months). The color and texture of each flap were satisfactory and each donor site exhibited a linear scar. Conclusions: Digital technology can effectively and precisely assist in the design and harvest of ALT lobulated perforator flaps, provide an effective approach for individualized evaluation and flap design and reduce the risk and difficulty of surgery.

A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism.

Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

Signatures of adaptation and purifying selection in highland populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland population identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

Van der Waals Magnetic Electrode Transfer for Two-Dimensional Spintronic Devices.

Two-dimensional (2D) materials are promising candidates for spintronic applications. Maintaining their atomically smooth interfaces during integration of ferromagnetic (FM) electrodes is crucial since conventional metal deposition tends to induce defects at the interfaces. Meanwhile, the difficulties in picking up FM metals with strong adhesion and in achieving conductance match between FM electrodes and spin transport channels make it challenging to fabricate high-quality 2D spintronic devices using metal transfer techniques. Here, we report a solvent-free magnetic electrode transfer technique that employs a graphene layer to assist in the transfer of FM metals. It also serves as part of the FM electrode after transfer for optimizing spin injection, which enables the realization of spin valves with excellent performance based on various 2D materials. In addition to two-terminal devices, we demonstrate that the technique is applicable for four-terminal spin valves with nonlocal geometry. Our results provide a promising future of realizing 2D spintronic applications using the developed magnetic electrode transfer technique.

5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation.

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management for sternal infection after midline sternotomy.

INTRODUCTION: Deep sternal wound infection (DSWI) after midline sternotomy of cardiac surgery is a challenging complication that affects the outcome of surgery. This study aims to assess the clinical effectiveness of the antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management in the treatment of DSWI. METHODS: We retrospectively analyzed 5 patients with DSWI who underwent antibiotic-loaded bone cement combined with bilateral pectoralis major muscle flaps for chest wall reconstruction after sternotomy for cardiac surgery in a tertiary hospital in China from January 2020 to December 2021. The clinical and follow-up data were retrospectively analyzed. RESULTS: All patients had no perioperative mortalities, no postoperative complications, 100% wound healing, and an average hospital stay length of 24 days. The follow-up periods were from 6 to 35 months (mean 19.6 months). None of the cases showed wound problems after initial reconstruction using antibiotic-loaded bone cement combined with bilateral pectoralis major muscle flaps. CONCLUSIONS: We report our successful treatment of DSWI, using antibiotic-loaded bone cement fixation technique combined with bilateral pectoralis major muscle flaps tension-free management. The clinical and follow-up results are favorable.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Sodium halide solid state electrolyte of Na3YBr6 with low activation energy.

Halide solid-state electrolytes (SSEs) are considered promising candidates for practical applications in all-solid-state batteries (ASSBs), due to their outstanding high voltage stability and compatibility with electrode materials. However, Na+ halide SSEs suffer from low ionic conductivity and high activation energy, which limit their applications in sodium all-solid-state batteries. Here, sodium yttrium bromide solid-state electrolytes (Na3YBr6) with a low activation energy of 0.15 eV is prepared via solid state reaction. Structure characterization using X-ray diffraction reveals a monoclinic structure (P21/c) of Na3YBr6. First principle calculations reveal that the low migration activation energy comes from the larger size and vibration of Br- anions, both of which expand the Na+ ion migration channel and reduce its activation energy. The electrochemical window of Na3YBr6 is determined to be 1.43 to 3.35 V vs. Na/Na+, which is slightly narrower than chlorides. This work indicates bromides are a good catholyte candidate for sodium all solid-state batteries, due to their low ion migration activation energy and relatively high oxidation stability.

Ant-eating spiders from Xizang, China (Araneae, Zodariidae).

Six species of the ant-eating spider of the family Zodariidae are described from Xizang, China, including five new species: Asceuachayusp. nov. (♀), A.dawaisp. nov. (♂♀), Mallinellamigusp. nov. (♂), M.mеdogsp. nov. (♂♀), and M.yadongsp. nov. (♂♀). The female of Cydrelalinzhiensis (Hu, 2001) is described here for the first time. Descriptions and photographs of all the species are provided.

Non-targeted mass spectrometry and feature-based molecular networking for determination of branched fatty acid esters of hydroxy fatty acids in milk.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) represent trace lipids with significant natural biological functions. While exogenous FAHFAs have been extensively studied, research on FAHFAs in milk remains limited, constraining our grasp of their nutritional roles. This study introduces a non-targeted mass spectrometry approach combined with chemical networking of spectral fragmentation patterns to uncover FAHFAs. Through meticulous sample handling and comparisons of various data acquisition and processing modes, we validate the method's superiority, identifying twice as many FAHFAs compared to alternative techniques. This validated method was then applied to different milk samples, revealing 45 chemical signals associated with known and potential FAHFAs, alongside findings of 66 ceramide/hexosylceramide (Cer/HexCer), 48 phosphatidyl ethanolamine/lyso phosphatidyl ethanolamine (PE/LPE), 21 phosphatidylcholine/lysophosphatidylcholine (PC/LPC), 16 phosphatidylinositol (PI), 7 phosphatidylserine (PS), and 11 sphingomyelin (SM) compounds. This study expands our understanding of the FAHFA family in milk and provides a fast and convenient method for identifying FAHFAs.

Sharp needle reconstructs peripheral outflow for patients with malfunctional arteriovenous fistula.

OBJECTIVE: To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients. METHODS: From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis. RESULTS: A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively. CONCLUSION: Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.

Flexible Sensor for Real-Time Monitoring of Motion Artifacts in Magnetic Resonance Imaging.

In recent years, magnetic resonance imaging has been widely used in the medical field. During the scan, if the human body moves, then there will be motion artifacts on the scan image, which will interfere with the diagnosis and only be found after the end of the scan sequence, resulting in a waste of manpower and resources. However, there is a lack of technology that halts scanning once motion artifacts arise. Here, we designed a real-time monitoring sensor (RMS) to dynamically perceive the movement of the human body and to pause in time when the movement exceeds a certain amplitude. The sensor has an array structure that can accurately sense the position of the human body in real time. The selection of the RMS ensures that there is no additional interference with the scanning results. Based on this design, the RMS can achieve the monitoring function of motion artifact generation.

Biomass-Based, Dual Enzyme-Responsive Nanopesticides: Eco-friendly and Efficient Control of Pine Wood Nematode Disease.

Pine wood nematode (PWN) disease is a globally devastating forest disease caused by infestation with PWN, Bursaphelenchus xylophilus, which mainly occurs through the vector insect Japanese pine sawyer (JPS), Monochamus alternatus. PWN disease is notoriously difficult to manage effectively and is known as the "cancer of pine trees." In this study, dual enzyme-responsive nanopesticides (AVM@EC@Pectin) were prepared using nanocoating avermectin (AVM) after modification with natural polymers. The proposed treatment can respond to the cell wall-degrading enzymes secreted by PWNs and vector insects during pine tree infestation to intelligently release pesticides to cut off the transmission and infestation pathways and realize the integrated control of PWN disease. The LC50 value of AVM@EC@Pectin was 11.19 mg/L for PWN and 26.31 mg/L for JPS. The insecticidal activity of AVM@EC@Pectin was higher than that of the commercial emulsifiable concentrate (AVM-EC), and the photostability, adhesion, and target penetration were improved. The half-life (t1/2) of AVM@EC@Pectin was 133.7 min, which is approximately twice that of AVM-EC (68.2 min). Sprayed and injected applications showed that nanopesticides had superior bidirectional transportation, with five-times higher AVM contents detected in the roots relative to those of AVM-EC when sprayed at the top. The safety experiment showed that the proposed treatment had lower toxicity and higher safety for nontarget organisms in the application environment and human cells. This study presents a green, safe, and effective strategy for the integrated management of PWN disease.

Corrigendum to "Optimization of a tannase-assisted process for obtaining teas rich in theaflavins from Camellia sinensis leaves" [Food Chemistry: X 13 (2022) 100203].

[This corrects the article DOI: 10.1016/j.fochx.2022.100203.].

Prognostic Value of Postoperative Complication for Gastric Cancer.

Background: The incidence of complications in gastric cancer (GC) patients after surgery was increasing, and it was not clear whether postoperative complications would have an impact on prognosis. The current study attempted to investigate the role of postoperative complication for prognosis on GC patients undergoing radical resection. Materials and Methods: Eligible studies were searched in three databases, including PubMed, Embase, and the Cochrane Library, in accordance with the searching strategy on September 4th, 2022. The survival values were most concerned; then, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled up. All prognostic values, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and recurrence-free survival (RFS), were allowed. Subgroup analysis based on complication types was used for further in-depth research. Results: A total of 29 studies involving 33,858 patients were included in this study. Intra-abdominal abscess (19.4%) was the most common complications in the included studies, followed by anastomotic leakage (17.0%) and pneumonia (16.4%). There were 23, 4, 6, and 10 studies that reported OS, DFS, DSS, and RFS, respectively. After analysis, postoperative complication was found to be an independent prognostic factor for OS (HR = 1.52, I2 = 1.14%, 95% CI = 1.42-1.61, P = .00), DFS (HR = 1.71, I2 = 0.00%,95% CI = 1.44-1.98, P < .05), DSS (HR = 1.60, I2 = 54.58%, 95% CI = 1.26-1.93, P < .1), and RFS (HR = 1.26, I2 = 0.00%, 95% CI = 1.11-1.41, P < .05). Subgroup analysis found that noninfectious complication was not significantly associated with OS (HR = 1.39, I2 = 0.00%, 95% CI = 0.96-1.82, P > .05). Conclusion: Surgeons needed to pay more attention to GC patients who developed postoperative complications, especially infectious complications, and take proactive management to improve the prognosis.

Insulin interacts with PPARγ agonists to promote bovine adipocyte differentiation.

Insulin is a potent adipogenic hormone that triggers a series of transcription factors that regulate the differentiation of preadipocytes into mature adipocytes. Ciglitazone specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. As a natural ligand of PPARγ, oleic acid (OA) can promote the translocation of PPARγ into the nucleus, regulate the expression of downstream genes, and promote adipocyte differentiation. We hypothesized that ciglitazone and oleic acid interact with insulin to enhance bovine preadipocyte differentiation. Preadipocytes were cultured 96 h in differentiation medium containing 10 mg/L insulin (I), 10 mg/L insulin + 10 µM cycloglitazone (IC), 10 mg/L insulin + 100 µM oleic acid (IO), or 10 mg/L insulin + 10 µM cycloglitazone+100 µM oleic acid (ICO). Control preadipocytes (CON) were cultured in differentiation medium (containing 5% fetal calf serum). The effects on the differentiation of Yanbian cattle preadipocytes were examined using molecular and transcriptomic techniques, including differentially expressed genes (DEGs) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. I, IC, IO, and ICO treatments produced higher concentrations of triglycerides (TAG) and lipid droplet accumulation in preadipocytes compared with CON treatment (P < 0.05). Co-treatment of insulin and PPARγ agonists significantly increased the expression of genes involved in regulating adipogenesis and fatty acid synthesis. (P < 0.05). Differential expression analysis identified 1488, 1764, 1974 and 1368 DEGs in the I, IC, IO and ICO groups, respectively. KEGG pathway analysis revealed DEGs mainly enriched in PPAR signalling, FOXO signaling pathway and fatty acid metabolism. These results indicate that OA, as PPARγ agonist, can more effectively promote the expression of bovine lipogenesis genes and the content of TAG and adiponectin when working together with insulin, and stimulate the differentiation of bovine preadipocytes. These findings provide a basis for further screening of relevant genes and transcription factors in intramuscular fat deposition and meat quality to enhance breeding programs.