A novel FAK-degrading PROTAC molecule exhibited both anti-tumor activities and efficient MDR reversal effects.

FAK (focal adhesion kinase) is widely involved in cancer growth and drug resistance development. Thus, FAK inhibition has emerged as an effective strategy for tumor treatment both as a monotherapy or in combination with other treatments. But the current FAK inhibitors mainly concentrate on its kinase activity, overlooking the potential significance of FAK scaffold proteins. In this study we employed the PROTAC technology, and designed a novel PROTAC molecule F2 targeting FAK based on the FAK inhibitor IN10018. F2 exhibited potent inhibitory activities against 4T1, MDA-MB-231, MDA-MB-468 and MDA-MB-435 cells with IC50 values of 0.73, 1.09, 5.84 and 3.05 µM, respectively. On the other hand, F2 also remarkably reversed the multidrug resistance (MDR) in HCT8/T, A549/T and MCF-7/ADR cells. Both the effects of F2 were stronger than the FAK inhibitor IN10018. To our knowledge, F2 was the first reported FAK-targeted PROTAC molecule exhibiting reversing effects on chemotherapeutic drug resistance, and its highest reversal fold could reach 158 times. The anti-tumor and MDR-reversing effects of F2 might be based on its inhibition on AKT (protein kinase B, PKB) and ERK (extracellular signal-regulated kinase) signaling pathways, as well as its impact on EMT (epithelial-mesenchymal transition). Furthermore, we found that F2 could reduce the protein level of P-gp in HCT8/T cells, thereby contributing to reverse drug resistance from another perspective. Our results will boost confidence in future research focusing on targeting FAK and encourage further investigation of PROTAC with potent in vivo effects.

Low-Coordinated Conductive ZnCu Metal-Organic Frameworks for Highly Selective H2O2 Electrosynthesis.

Direct electrosynthesis of hydrogen peroxide (H2O2) with high production rate and high selectivity through the two-electron oxygen reduction reaction (2e-ORR) offers a sustainable alternative to the energy-intensive anthraquinone technology but remains a challenge. Herein, a low-coordinated, 2D conductive Zn/Cu metal-organic framework supported on hollow nanocube structures (ZnCu-MOF (H)) is rationally designed and synthesized. The as-prepared ZnCu-MOF (H) catalyst exhibits substantially boosted electrocatalytic kinetics, enhanced H2O2 selectivity, and ultra-high Faradaic efficiency for 2e-ORR process in both alkaline and neutral conditions. Electrochemical measurements, operando/quasi in situ spectroscopy, and theoretical calculation demonstrate that the introduction of Cu atoms with low-coordinated structures induces the transformation of active sites, resulting in the beneficial electron transfer and the optimized energy barrier, thereby improving the electrocatalytic activity and selectivity.

Coffee, tea, and cocoa in obesity prevention: Mechanisms of action and future prospects.

Obesity, a major public health problem, causes numerous complications that threaten human health and increase the socioeconomic burden. The pathophysiology of obesity is primarily attributed to lipid metabolism disorders. Conventional anti-obesity medications have a high abuse potential and frequently deliver insufficient efficacy and have negative side-effects. Hence, functional foods are regarded as effective alternatives to address obesity. Coffee, tea, and cocoa, three widely consumed beverages, have long been considered to have the potential to prevent obesity, and several studies have focused on their intrinsic molecular mechanisms in past few years. Therefore, in this review, we discuss the mechanisms by which the bioactive ingredients in these three beverages counteract obesity from the aspects of adipogenesis, lipolysis, and energy expenditure (thermogenesis). The future prospects and challenges for coffee, tea, and cocoa as functional products for the treatment of obesity are also discussed, which can be pursued for future drug development and prevention strategies against obesity.

Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function.

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.

ATP6AP2, a regulator of LRP6/ß-catenin protein trafficking, promotes Wnt/ß-catenin signaling and bone formation in a cell type dependent manner.

Wnt/ß-catenin signaling is critical for various cellular processes in multiple cell types, including osteoblast (OB) differentiation and function. Exactly how Wnt/ß-catenin signaling is regulated in OBs remain elusive. ATP6AP2, an accessory subunit of V-ATPase, plays important roles in multiple cell types/organs and multiple signaling pathways. However, little is known whether and how ATP6AP2 in OBs regulates Wnt/ß-catenin signaling and bone formation. Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions. Conditionally knocking out (CKO) ATP6AP2 in the OB-lineage cells (Atp6ap2Ocn-Cre) reduced trabecular, but not cortical, bone formation and bone mass. Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs, but not osteocytes. Additional in vitro and in vivo studies revealed impaired ß-catenin signaling in ATP6AP2-KO BMSCs and OBs, but not osteocytes, under both basal and Wnt stimulated conditions, although LRP5 was decreased in ATP6AP2-KO osteocytes, but not BMSCs. Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression of ß-catenin phosphorylation, but necessary for LRP6/ß-catenin and N-cadherin/ß-catenin protein complex distribution at the cell membrane, thus preventing their degradation. Expression of active ß-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs. Taken together, these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability, and thus regulating ß-catenin levels, demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/ß-catenin signaling and trabecular bone formation.

Enhancing the energetic and magnetic stability of atomic hydrogen chemisorbed on graphene using (non)compensated B-N pairs.

In this pioneering study for identifying atomic scale magnetic moment, a single hydrogen atom chemisorbed on pristine graphene exhibits distinct spin polarization. Using first-principles calculations and analyses, we demonstrate that the binding between a H adsorbate and a C substrate is substantially enhanced via compensated B-N pairs embedded into graphene. Surprisingly, the interaction can be further enhanced via non-compensated B-N pair doping. Our established prototype of orbital intercoupling between H 1s and hybridized pz of gapped band edges gives an insight into the enhancing mechanism. For compensated B-N doping, the conduction band minimum (CBM) is pushed upward, which induces stronger interaction between the H 1s and hybridized pz orbitals of the CBM. For non-compensated B-N doping, the orbital interaction occurs between H 1s and hybridized pz orbitals of valence band maximum, thus further lowering the resulting bonding energy due to the enlarged gap. This significantly enhanced interaction between H and C atoms agrees well with the results of charge localization at the gapped band edges. More importantly, the corresponding magnetic moments can be well maintained or even enhanced in both doping; here, one more H atom is needed for non-compensated doping, where its electron occupies the empty CBM. Our findings might provide an effective and practical way to enhance the energetic and magnetic stability of atomic scale magnetic moment on graphene and extensively expand the conception of non-compensated doping.

Progress of engineered bacteria for tumour therapy.

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.

Mechanistic insights into diversified photoluminescence behaviours of BF2 complexes of N-benzoyl 2-aminobenzothiazoles.

Many BF2 complexes of heteroaromatics are well known for their dual-state emission (DSE) properties. However, AIE and ACQ effects have also been observed in certain cases. To date, no rational explanations have been proposed for these uncommon photoluminescence (PL) behaviours. The current research prepared four BF2 complexes of N-benzoyl 2-aminobenzothiazoles with diversified photoluminescence (PL) properties as model compounds and utilized quantum chemical calculation tools to address this issue. Theoretical calculations revealed that the electron-donating groups (EDGs) at the para-position of the exocyclic phenyl ring exert significant influence on their ground-state electronic structures and vertical excitation features. Potential energy curve (PEC) analysis showed that the exocyclic phenyl ring and NMe2 could not function as effective rotors due to elevated energy barriers. Only the NPh2 of BFBB-3 could spontaneously rotate ∼60° to induce the formation of an emissive twisted intramolecular charge transfer (TICT) state. The two-channel model involving both vibronic relaxation and S0/S1 surface crossing revealed that the drastic narrowing of the S1/S0 energy gap in the region approaching minimun energy conical intersection (MECI) led to the generation of a dark state in BFBB-1. The small energy barrier to access the dark-state region makes the resulting fast internal conversion a competitive channel for excited-state deactivation. In contrast, the presence of EDGs in BFBB-2 and 4 inhibits this pathway, thereby resulting in intense fluorescence emissions in solution. In addition, crystallographic analysis illustrated that the F atoms perpendicular to the polyheterocycle promoted a slipped face-to-face packing mode and enhanced intermolecular interactions. The efficiencies of their solid-state emissions are mainly affected by the degree of π-π overlaps.

Importance of the Posterior Plate in Three-Column Tibial Plateau Fractures: A Finite Element Analysis and Clinical Validation.

OBJECTIVE: Dual-plate fixation was thought to be the gold standard for treating complicated bicondylar tibial plateau fractures, yet it was found to be hard to accommodate the posterior column in three-column fractures. Currently, column-specific fixation is becoming more and more recognized, but no comprehensive investigation has been performed to back it up. Therefore, the objective of this study was to validate the importance of posterior column fixation in the three-column tibial fractures by a finite element (FE) analysis and clinical study. METHODS: In FE analysis, three models were developed: the longitudinal triple-plate group (LTPG), the oblique triple-plate group (OTPG), and the dual-plate group (DPG). Three loading scenarios were simulated. The distribution of the displacement and the equivalent von Mises stress (VMS) in each structure was calculated. The comparative measurements including the maximum posterior column collapse (MPCC), the maximum total displacement of the model (MTD), the maximum VMS of cortical posterior column (MPC-VMS), and the maximum VMS located on each group of plates and screws (MPS-VMS). The clinical study evaluated the indicators between the groups with or without the posterior plate, including operation time, blood loss volume, full-weight bearing period, Hospital for Special Surgery Knee Scoring system (HSS), Rasmussen score, and common postoperative complications. RESULTS: In the FE analysis, the MPCC, the MPC-VMS, and the MTD were detected in much lower amounts in LTPG and OTPG than in DPG. In comparison with DPG, the LTPG and OTPG had larger MPS-VMS. In the clinical study, 35 cases were included. In the triple-plate (14) and dual-plate (21) groups, the operation took 115.6 min and 100.5 min (p < 0.05), respectively. Blood loss in both groups was 287.0 mL and 206.6 mL (p < 0.05), and the full-weight bearing period was 14.5 weeks and 16.2 weeks (p < 0.05). At the final follow-up, the HSS score was 85.0 in the triple-plate group and 77.5 in the dual-plate (p < 0.05), the Rasmussen score was 24.1 and 21.6 (p < 0.05), there were two cases with reduction loss (9.5%) in the dual-plate group and one case of superficial incision infection found in the triple-plate group. CONCLUSION: The posterior implant was beneficial in optimizing the biomechanical stability and functional outcomes in the three-column tibial plateau fractures.

Therapeutic Potential of Danyankang Capsule in High-Fat Diet-Induced Cholelithiasis and Its Impact on Liver FXR Signaling and Gut Microbiota.

Cholelithiasis, commonly known as gallstones, represents a prevalent hepatobiliary disorder. This study aimed to elucidate the therapeutic role and mechanism of Danyankang capsulein treating cholelithiasis induced by a high-fat diet in C57BL/6 mice. The therapeutical potential of Danyankang was assessed through biochemical analyses, histopathological examinations, protein detection, and 16S rDNA sequencing. A high-fat diet resulted in cholelithiasis manifestation in mice, with discernable abnormal serum biochemical indices and disrupted biliary cholesterol homeostasis. Danyankang treatment notably ameliorated liver inflammation symptoms and rectified serum and liver biochemical abnormalities. Concurrently, it addressed biliary imbalances. Elevated expressions of toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB)/pNF-κB, HMGCR, CYP7A1, and CYP8B1 observed at the inception of cholelithiasis, were notably reduced upon Danyankang administration. Furthermore, 16S rDNA analysis revealed a decline in species number and diversity of the intestinal flora in cholelithiasis-treated mice, while the decline was reversed with Danyankang treatment. Danyankang capsules reduced the abundance of Verrucomicrobiota and increased the abundance of Actinobacteriota and Proteobacteria. In conclusion, the present study demonstrates that Danyankang exerts potent therapeutic efficacy against high-fat diet-induced cholelithiasis. This beneficial outcome is potentially linked to the inhibition of the TLR4/pNF-κB and SHP/CYP7A1/CYP8B1 signaling pathways, as well as the enhancement of intestinal flora species abundance.

Effect of salting and dehydration treatments on the physicochemical and gel properties of hen and duck egg yolks, plasma and granules.

BACKGROUND: Salted hen egg yolks are less oily and less flavorful than salted duck egg yolks. However, hen eggs have a more adequate market supply and have a broader application prospect than duck eggs. In the present study, egg yolks, plasma, and granules were dehydrated by adding 1% NaCl to simulate traditional curing process of salted egg yolk. The changes in the pickling process of hen egg yolks (HEY) and duck egg yolks (DEY) plasma and granules were compared to reveal the gelation mechanism and the underlying causes of quality differences in salted HEY and DEY. Salted HEY can be compared with the changes in DEY during the pickling process to provide a theoretical basis for the quality improvement of salted HEY to salted DEY. RESULTS: The results showed that both plasma and granules were involved in gel formation, but exhibited different aggregation behaviors. Based on the intermolecular forces, the HEY proteins achieved aggregation mainly through hydrophobic interactions and DEY proteins mainly through covalent binding. According to spin-spin relaxation time, HEY gels immobilized a large amount of lipid and interacted strongly with lipids. DEY gels showed much free lipid and had weak interaction with lipid. The microstructure showed that HEY proteins were easily unfolded to form a homogeneous three-dimensional gel network structure after salting, whereas heterogeneous aggregates were formed to hinder the gel development in DEY. Changes in protein secondary structure content showed that pickling can promote the transformation of the α-helices to ß-sheets structure in HEY gels, whereas more α-helices structure was formed in DEY gels. CONCLUSION: The present study has demonstrated that different gelation behaviors of hen and duck egg yolk proteins (especially in plasma) through salting treatment led to the difference in the quality of salted HEY and DEY. © 2024 Society of Chemical Industry.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides.

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.

Macrophage ß-arrestin-1 deteriorates DSS-induced colitis through interaction with NF-κB signaling.

ß-arrestin-1 has been demonstrated to participate in the regulation of inflammatory reactions in several diseases. Thus, this study aimed to investigate the role of macrophage ß-arrestin-1 in the pathogenesis and progression of ulcerative colitis (UC). A myeloid ß-arrestin-1 conditional knockout mouse model was generated to explore the role of macrophage ß-arrestin-1. DSS was employed for the establishment of an ulcerative colitis mouse model, using TNF-α as an inflammatory stressor in vitro. The expression level of ß-arrestin-1 was detected via western blot and immunofluorescence assays, whilst disease severity was evaluated by clinical score and H&E staining in the DSS-induced colitis model. In the in vitro experiments, the levels of inflammatory cytokines were examined using real-time PCR. NF-κB activation was detected through the double luciferase reporter system, western blot, and electrophoretic mobility shift assay (EMSA). BAY11-7082 was used to inhibit NF-κB activation. Our results exposed that the level of ß-arrestin-1 was increased in monocytes/macrophages derived from DSS-induced colitis mice or under the TNF-α challenge. Moreover, conditionally knocking out the expression of myeloid ß-arrestin-1 alleviated disease severity, while knocking out the expression of ß-arrestin-1 decreased the levels of inflammatory cytokines. Additionally, NF-κB was identified as a central regulatory element of ß-arrestin-1 promoter, and using BAY11-7082 to inhibit NF-κB activation lowered the level of ß-arrestin-1 under TNF-α challenge. ß-arrestin-1 led to the activation of the NF-κB signaling pathway by enhancing binding to IκBα and IKK under the TNF-α challenge. Taken together, our findings demonstrated macrophage ß-arrestin-1 contributes to the deterioration of DSS-induced colitis through the interaction with NF-κB signaling, thus highlighting a novel target for the treatment of UC.

Oxygen-Activated Boron Nitride for Selective Photocatalytic Coupling of Methanol to Ethylene Glycol.

The controllable photocatalytic C-C coupling of methanol to produce ethylene glycol (EG) is a highly desirable but challenging objective for replacing the current energy-intensive thermocatalytic process. Here, we develop a metal-free porous boron nitride catalyst that demonstrates exceptional selectivity in the photocatalytic production of EG from methanol under mild conditions. Comprehensive experiments and calculations are conducted to thoroughly investigate the reaction mechanism, revealing that the OB3 unit in the porous BN plays a critical role in the preferential activation of C-H bond in methanol to form ⋅CH2OH via a concerted proton-electron transfer mechanism. More prominent energy barriers are observed for the further dehydrogenation of the ⋅CH2OH intermediate on the OB3 unit, inhibiting the formation of some other by-products during the catalytic process. Additionally, a small downhill energy barrier for the coupling of ⋅CH2OH in the OB3 unit promotes the selective generation of EG. This study provides valuable insights into the underlying mechanisms and can serve as a guide for the design and optimization of photocatalysts for efficient and selective EG production under mild conditions.

Utilization of cannulated screw fixation of Jail and TiRobot-assisted percutaneous indirect reduction technique for AO/OTA type 41B2 tibial plateau fracture treatment.

PURPOSE: The present study was designed to investigate the precise procedure and effectiveness of percutaneous minimally invasive fixation assisted by TiRobot in managing AO/OTA type 41B2 tibial plateau fracture to provide an alternative solution for clinical application. METHODS: In total, 10 participants with AO/OTA type 41B2 tibial plateau fractures diagnosed by preoperative imaging examinations were enrolled in this study between May 2019 and May 2022. They were 5 males and 5 females, with an average age of 45.6 ± 11.3 years old (range 27-62 years old). All of them had closed fractures, including 6 cases with anterior cruciate ligament (ACL) tibial insertion avulsion fractures, 1 case with medial collateral ligament (MCL) tear, and 4 cases with a lateral meniscus tear. From injury through surgery, the entire time frame was 4.0 ± 1.5 days (range, 2-7 days). Following indirect percutaneous reduction assisted by TiRobot, the Jail method was used to treat all patients with minimally invasive internal fixation. Patients with ligament or meniscus injurieswere treated with arthroscopic surgery in one stage. The standardized functional exercise was performed postoperatively. The knee function was measured using the Hospital for Special Surgery (HSS) score, and the fracture reduction was assessed through the Rasmussen radiology score. RESULTS: All patients were followed up for 12.7 ± 6.8 months (6-24 months).The fracture healing time was 11.8 ± 0.8 weeks (10-13 weeks), and the X-rays revealed satisfactory fracture reduction.The knee joint's Rasmussen score was 17.8 ± 0.4 (in the range of 17-18) a year after the procedure, with 8 patients receiving outstanding ratings and 2 cases receiving satisfactory scores. The HSS score was 93.8 ± 2.3 (range, 89 to 96), of which 10 cases were excellent. The motion range of the kneewas 138.7°±2.7° (range, -5° to 0° to 135°). No adverse effects or serious complications, such as internal fixation failure, postoperative infection, popliteal vascular injury, and common peroneal nerve injury, were observed during the last follow-up visit. CONCLUSIONS: The intelligent assistance and accurate guidance of TiRobot can simplify and standardize procedures of percutaneous minimally invasive fixation in theSchatzker type Ⅲ tibial plateau fracture treatment. This technique increases the precision of indirect percutaneous reduction and screw fixation while minimizing bone grafting.

Selective Electrocatalytic Conversion of Nitric Oxide to High Value-Added Chemicals.

The artificial disturbance in the nitrogen cycle has necessitated an urgent need for nitric oxide (NO) removal. Electrochemical technologies for NO conversion have gained increasing attention in recent years. This comprehensive review presents the recent advancements in selective electrocatalytic conversion of NO to high value-added chemicals, with specific emphasis on catalyst design, electrolyte composition, mass diffusion, and adsorption energies of key intermediate species. Furthermore, the review explores the synergistic electrochemical co-electrolysis of NO with specific carbon source molecules, enabling the synthesis of a range of valuable chemicals with C─N bonds. It also provides in-depth insights into the intricate reaction pathways and underlying mechanisms, offering valuable perspectives on the challenges and prospects of selective NO electrolysis. By advancing comprehension and fostering awareness of nitrogen cycle balance, this review contributes to the development of efficient and sustainable electrocatalytic systems for the selective synthesis of valuable chemicals from NO.

Triple-Phase Photocatalytic H2O2 Production on a Janus Fiber Membrane with Asymmetric Hydrophobicity.

Photocatalytic O2 reduction is an intriguing approach to producing H2O2, but its efficiency is often hindered by the limited solubility and mass transfer of O2 in the aqueous phase. Here, we design and fabricate a two-layered (2L) Janus fiber membrane photocatalyst with asymmetric hydrophobicity for efficient photocatalytic H2O2 production. The top layer of the membrane consists of superhydrophobic polytetrafluoroethylene (PTFE) fibers with a dispersed modified carbon nitride (mCN) photocatalyst. Amphiphilic Nafion (Naf) ionomer is sprayed onto this layer to modulate the microenvironment and achieve moderate hydrophobicity. In contrast, the bottom layer consists of bare PTFE fibers with high hydrophobicity. The elaborate structural configuration and asymmetric hydrophobicity feature of the optimized membrane photocatalyst (designated as 2L-mCN/F-Naf; F, PTFE) allow most mCN to be exposed with gas-liquid-solid triple-phase interfaces and enable rapid mass transfer of gaseous O2 within the hierarchical membrane, thus increasing the local O2 concentration near the mCN photocatalyst. As a result, the optimized 2L-mCN/F-Naf membrane photocatalyst shows remarkable photocatalytic H2O2 production activity, achieving a rate of 5.38 mmol g-1 h-1 under visible light irradiation.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .