Scavenger receptor B2, a type III membrane pattern recognition receptor, senses LPS and activates the IMD pathway in crustaceans.

The immune deficiency (IMD) pathway is critical for elevating host immunity in both insects and crustaceans. The IMD pathway activation in insects is mediated by peptidoglycan recognition proteins, which do not exist in crustaceans, suggesting a previously unidentified mechanism involved in crustacean IMD pathway activation. In this study, we identified a Marsupenaeus japonicus B class type III scavenger receptor, SRB2, as a receptor for activation of the IMD pathway. SRB2 is up-regulated upon bacterial challenge, while its depletion exacerbates bacterial proliferation and shrimp mortality via abolishing the expression of antimicrobial peptides. The extracellular domain of SRB2 recognizes bacterial lipopolysaccharide (LPS), while its C-terminal intracellular region containing a cryptic RHIM-like motif interacts with IMD, and activates the pathway by promoting nuclear translocation of RELISH. Overexpressing shrimp SRB2 in Drosophila melanogaster S2 cells potentiates LPS-induced IMD pathway activation and diptericin expression. These results unveil a previously unrecognized SRB2-IMD axis responsible for antimicrobial peptide induction and restriction of bacterial infection in crustaceans and provide evidence of biological diversity of IMD signaling in animals. A better understanding of the innate immunity of crustaceans will permit the optimization of prevention and treatment strategies against the arising shrimp diseases.

Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

White spot syndrome virus directly activates mTORC1 signaling to facilitate its replication via polymeric immunoglobulin receptor-mediated infection in shrimp.

Previous studies have shown that the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway has antiviral functions or is beneficial for viral replication, however, the detail mechanisms by which mTORC1 enhances viral infection remain unclear. Here, we found that proliferation of white spot syndrome virus (WSSV) was decreased after knockdown of mTor (mechanistic target of rapamycin) or injection inhibitor of mTORC1, rapamycin, in Marsupenaeus japonicus, which suggests that mTORC1 is utilized by WSSV for its replication in shrimp. Mechanistically, WSSV infects shrimp by binding to its receptor, polymeric immunoglobulin receptor (pIgR), and induces the interaction of its intracellular domain with Calmodulin. Calmodulin then promotes the activation of protein kinase B (AKT) by interaction with the pleckstrin homology (PH) domain of AKT. Activated AKT phosphorylates mTOR and results in the activation of the mTORC1 signaling pathway to promote its downstream effectors, ribosomal protein S6 kinase (S6Ks), for viral protein translation. Moreover, mTORC1 also phosphorylates eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which will result in the separation of 4EBP1 from eukaryotic translation initiation factor 4E (eIF4E) for the translation of viral proteins in shrimp. Our data revealed a novel pathway for WSSV proliferation in shrimp and indicated that mTORC1 may represent a potential clinical target for WSSV control in shrimp aquaculture.

Theoretical Insights into the Mechanism and Origin of Solvent-Dependent Selectivity in the Cyclization of Propargyl Alcohols for the Divergent Synthesis of N-Heterocycles.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF3•OEt2-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF3, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF2•DMF]+, formed from DMF and BF3•OEt2, acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF4- formation from DMF and BF3•OEt2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

Ulnar lengthening for children with forearm deformity from hereditary multiple exostoses: a retrospective study from a tertiary medical center.

BACKGROUND: Patients with hereditary multiple exostosis (HME) usually present with forearm deformity with or without radial head dislocation. Ulna lengthening has been proposed to address this condition. Exostosis resection plus ulna lengthening has been adopted in our hospital since 2008, and patients with this condition were retrospectively reviewed. Herein, we aimed to investigate the optimal timing and clinical outcomes of this surgical approach. METHODS: In all, thirty-five patients (40 forearms), including 22 boys and 13 girls, were enrolled in our study from July 2014 to September 2020. We divided the patients into 4 groups based on the age when they received surgery and the status of the radial head. Pronation and supination of the forearm, flexion and extension of the elbow, wrist ulnar deviation and wrist radial deviation, and radiological parameters including ulnar length (UL), ulnar variance (UV), the percentage of radial bowing (RB/RL), radio articular angle (RAA) and carpal slip (CS), were assessed and recorded. RESULTS: The mean UL was significantly improved after surgery in four Groups (P<0.05). In patients with radial head dislocation, we found significant improvement in forearm, wrist function and elbow flexion (p < 0.05). For the patients with radial head dislocation, the juniors demonstrated better improvement in % RB and RAA (p<0.05, p = 0.003 and 0.031). CONCLUSION: Exostosis resection and ulna lengthening with unilateral external fixation can effectively improve the function and radiological parameters of forearm deformity in HME children. For patients with radial head dislocation, early surgery can achieve better results. For patients not associated with radial head dislocation, we recommend regular follow-up and surgical treatment after 10 years of age.

Enhanced recovery after surgery in patients after hip and knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Enhanced recovery after surgery (ERAS) was characterized as patient-centered, evidence-based, multidisciplinary team-developed routes for a surgical speciality and institution to improve postoperative recovery and attenuate the surgical stress response. However, evidence of their effectiveness in osteoarthroplasty remains sparse. This study aimed to develop an ERAS standard and evaluate the significance of ERAS interventions for postoperative outcomes after primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: We searched Medline, Embase, Cochrane databases, and Clinicaltrials.gov for randomized controlled trials, cohort studies, and case-control studies until 24 February 2023. All relevant data were collected from studies meeting the inclusion criteria. Two reviewers independently assessed the risk of bias and extracted data. The primary outcome was the length of stay (LOS), postoperative complications, and readmission rate. The secondary outcomes included transfusion rate, mortality rate, visual analog score (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Short Form 36 (SF-36) bodily pain (SF-36 BP), SF-36 physical function (SF-36 PF), oxford knee score, and range of motion (ROM). RESULTS: A total of 47 studies involving 76 971 patients (ERAS group: 29 702, control group: 47 269) met the inclusion criteria and were included in the meta-analysis. The result showed that ERAS could significantly shorten the LOS (WMD = -2.65, P < .001), reduce transfusion rate (OR = 0.40, P < .001), and lower 30-day postoperative mortality (OR = 0.46, P = .01) without increasing postoperative complications or readmission rate. Apart from that, ERAS may decrease patients' VAS (WMD = -0.88, P = .01) while improving their ROM (WMD = 6.65, P = .004), SF-36 BP (WMD = 4.49, P < .001), and SF-36 PF (WMD = 3.64, P < .001) scores. However, there was no significant difference in WOMAC, oxford knee score between the ERAS and control groups.Furthermore, we determined that the following seven components of the ERAS program are highly advised: avoid bowel preparation, PONV prophylaxis, standardized anesthesia, use of local anesthetics for infiltration analgesia and nerve blocks, tranexamic acid, prevent hypothermia, and early mobilization. CONCLUSION: Our meta-analysis suggested that the ERAS could significantly shorten the LOS, reduce transfusion rate, and lower 30-day postoperative mortality without increasing postoperative complications or readmission rate after THA and TKA. Meanwhile, ERAS could decrease the VAS of patients while improving their ROM, SF-36 BP, and SF-36 PF scores. Finally, we expect future studies to utilize the seven ERAS elements proposed in our meta-analysis to prevent increased readmission rate for patients with THA or TKA.

Towards Optical Information Recording: A Robust Visible-Light-Driven Molecular Photoswitch with the Ring-Closure Reaction Yield Exceeding 96.3 .

Diarylethene molecular photoswitches hold great fascination as optical information materials due to their unique bistability and exceptional reversible photoswitching properties. Conventional diarylethenes, however, rely on UV light for ring-closure reactions, typically with modest yields. For practical application, diarylethenes driven by visible lights are preferred but achieving high ring-closure reaction yield remains a significant challenge. Herein, we synthesized a novel all-visible-light-driven photoswitch, TPAP-DTE, by facilely endcapping the dithienylethene (DTE) core with triphenylamine phenyl (TPAP) groups. Owing to the electron-donating conjugation effect of TPAP, the open-form TPAP-DTE responds strongly to short-wavelength visible lights with considerable photocyclization quantum yields and molar absorption coefficient. Upon 405 nm visible-light irradiation, TPAP-DTE achieves a ring-closure reaction yield exceeding 96.3 % (confirmed by both nuclear magnetic resonance spectroscopy and high-performance liquid chromatography). Its ring-opening reaction yield is 100 % upon irradiation with long-wavelength visible light. TPAP-DTE could be regarded as a bidirectional "quasi"-quantitative conversion molecular switch. Furthermore, TPAP-DTE exhibits robust fatigue resistance over 100 full photoswitching cycles and great anti-aging property under 85 °C and 85 % humidity for at least 1000 h. Consequently, its rewritable QR-code, multilevel data storage, and anti-counterfeiting/encryption applications are successfully demonstrated exclusively using visible lights, positioning TPAP-DTE as a highly promising medium for information recording.

T-cell senescence: A crucial player in autoimmune diseases.

Senescent T cells are proliferative disabled lymphocytes that lack antigen-specific responses. The development of T-cell senescence in autoimmune diseases contributes to immunological disorders and disease progression. Senescent T cells lack costimulatory markers with the reduction of T cell receptor repertoire and the uptake of natural killer cell receptors. Senescent T cells exert cytotoxic effects through the expression of perforin, granzymes, tumor necrosis factor, and other molecules without the antigen-presenting process. DNA damage accumulation, telomere damage, and limited DNA repair capacity are important features of senescent T cells. Impaired mitochondrial function and accumulation of reactive oxygen species contribute to T cell senescence. Alleviation of T-cell senescence could provide potential targets for the treatment of autoimmune diseases.

FOXO regulates the expression of antimicrobial peptides and promotes phagocytosis of hemocytes in shrimp antibacterial immunity.

Invertebrates rely on innate immunity, including humoral and cellular immunity, to resist pathogenic infection. Previous studies showed that forkhead box transcription factor O (FOXO) participates in mucosal immune responses of mammals and the gut humoral immune regulation of invertebrates. However, whether FOXO is involved in systemic and cellular immunity regulation in invertebrates remains unknown. In the present study, we identified a FOXO from shrimp (Marsupenaeus japonicus) and found that it was expressed at relatively basal levels in normal shrimp, but was upregulated significantly in shrimp challenged by Vibrio anguillarum. FOXO played a critical role in maintaining hemolymph and intestinal microbiota homeostasis by promoting the expression of Relish, the transcription factor of the immune deficiency (IMD) pathway for expression of antimicrobial peptides (AMPs) in shrimp. We also found that pathogen infection activated FOXO and induced its nuclear translocation by reducing serine/threonine kinase AKT activity. In the nucleus, activated FOXO directly regulated the expression of its target Amp and Relish genes against bacterial infection. Furthermore, FOXO was identified as being involved in cellular immunity by promoting the phagocytosis of hemocytes through upregulating the expression of the phagocytotic receptor scavenger receptor C (Src), and two small GTPases, Rab5 and Rab7, which are related to phagosome trafficking to the lysosome in the cytoplasm. Taken together, our results indicated that FOXO exerts its effects on homeostasis of hemolymph and the enteric microbiota by activating the IMD pathway in normal shrimp, and directly or indirectly promoting AMP expression and enhancing phagocytosis of hemocytes against pathogens in bacteria-infected shrimp. This study revealed the different functions of FOXO in the mucosal (local) and systemic antibacterial immunity of invertebrates.

Metabolomic Profiles in the Intestine of Shrimp Infected by White Spot Syndrome Virus and Antiviral Function of the Metabolite Linoleic Acid in Shrimp.

White spot syndrome virus (WSSV) is a threatening pathogenic virus in shrimp culture, and at present, no effective strategy can prevent and control the disease. Intestinal flora and its metabolites are important for the resistance of shrimp to lethal pathogenic viruses. However, the changes of metabolites in the shrimp intestines after WSSV infection remain unclear. We established an artificial oral infection method to infect shrimp with WSSV and analyzed the metabolites in intestinal content of shrimp by HPLC and tandem mass spectrometry. A total of 78 different metabolites and five different metabolic pathways were identified. Among them, we found that the content of linoleic acid, an unsaturated fatty acid, increased significantly after WSSV infection, indicating that linoleic acid might be involved in antiviral immunity in shrimp. Further study showed that, after oral administration of linoleic acid, WSSV proliferation decreased evidently in the shrimp, and survival rate of the shrimp increased significantly. Mechanical analysis showed that linoleic acid directly bound to WSSV virions and inhibited the viral replication. Linoleic acid also promoted the expression of antimicrobial peptides and IFN-like gene Vago5 by activating the ERK-NF-κB signaling pathway. Our results indicated that WSSV infection caused metabolomic transformation of intestinal microbiota and that the metabolite linoleic acid participated in the immune response against WSSV in shrimp.

Gene Mutations and Targeted Therapies of Myeloid Sarcoma.

OPINION STATEMENT: Myeloid sarcoma, a rare malignant tumor characterized by the invasion of extramedullary tissue by immature myeloid cells, commonly occurs concomitantly with acute myeloid leukemia, myelodysplastic syndromes, or myeloproliferative neoplasms. The rarity of myeloid sarcoma poses challenges for diagnosis and treatment. Currently, treatments for myeloid sarcoma remain controversial and primarily follow protocols for acute myeloid leukemia, such as chemotherapy utilizing multi-agent regimens, in addition to radiation therapy and/or surgery. The advancements in next-generation sequencing technology have led to significant progress in the field of molecular genetics, resulting in the identification of both diagnostic and therapeutic targets. The application of targeted therapeutics, such as FMS-like tyrosine kinase 3(FLT3) inhibitors, isocitrate dehydrogenases(IDH) inhibitors, and the B cell lymphoma 2(BCL2) inhibitors, has facilitated the gradual transformation of traditional chemotherapy into targeted precision therapy for acute myeloid leukemia. However, the field of targeted therapy for myeloid sarcoma is relatively under-investigated and not well-described. In this review, we comprehensively summarize the molecular genetic characteristics of myeloid sarcoma and the current application of targeted therapeutics.

Molecular mechanism and therapeutic potential of HDAC9 in intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is the major cause of low-back pain. Histone deacetylase 9 (HDAC9) was dramatically decreased in the degenerative nucleus pulposus (NP) samples of patients with intervertebral disc degeneration (IVDD) according to bioinformatics analysis of Gene Expression Omnibus (GEO) GSE56081 dataset. This study aims to investigate the role of HDAC9 in IVDD progression. METHODS: The contribution of HDAC9 to the progression of IVDD was assessed using HDAC9 knockout (HDAC9KO) mice and NP-targeted HDAC9-overexpressing mice by IVD injection of adenovirus-mediated HDAC9 under a Col2a1 promoter. Magnetic resonance imaging (MRI) and histological analysis were used to examine the degeneration of IVD. NP cells were isolated from mice to investigate the effects of HDAC9 on apoptosis and viability. mRNA-seq and coimmunoprecipitation/mass spectrometry (co-IP/MS) analysis were used to analyze the HDAC9-regulated factors in the primary cultured NP cells. RESULTS: HDAC9 was statistically decreased in the NP tissues in aged mice. HDAC9KO mice spontaneously developed age-related IVDD compared with wild-type (HDAC9WT) mice. In addition, overexpression of HDAC9 in NP cells alleviated IVDD symptoms in a surgically-induced IVDD mouse model. In an in vitro assay, knockdown of HDAC9 inhibited cell viability and promoted cell apoptosis of NP cells, and HDAC9 overexpression had the opposite effects in NP cells isolated from HDAC9KO mice. Results of mRNA-seq and co-IP/MS analysis revealed the possible proteins and signaling pathways regulated by HDAC9 in NP cells. RUNX family transcription factor 3 (RUNX3) was screened out for further study, and RUNX3 was found to be deacetylated and stabilized by HDAC9. Knockdown of RUNX3 restored the effects of HDAC9 silencing on NP cells by inhibiting apoptosis and increasing viability. CONCLUSION: Our results suggest that HDAC9 plays an important role in the development and progression of IVDD. It might be required to protect NP cells against the loss of cell viability and apoptosis by inhibiting RUNX3 acetylation and expression during IVDD. Together, our findings suggest that HDAC9 may be a potential therapeutic target in IVDD.

Targeting HSP90 with picropodophyllin suppresses gastric cancer tumorigenesis by disrupting the association of HSP90 and AKT.

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Thus, the development of safe and effective therapeutic compounds for GC treatment is urgently required. Here, we aimed to examine the role of picropodophyllin (PPP), a compound extracted from the rhizome of Dysosma versipellis (Hance) M. Cheng ex Ying, on the proliferation of GC cells. Our study revealed that PPP inhibits the proliferation of GC cells in a dose-dependent manner by inducing apoptosis. Moreover, our study elucidated that PPP suppresses the growth of GC tumor xenografts with no side effects of observable toxicity. Mechanistically, PPP exerts its effects by blocking the AKT/mammalian target of rapamycin (mTOR) signaling pathway; these effects are markedly abrogated by the overexpression of constitutively active AKT. Furthermore, drug affinity responsive target stability (DARTS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) revealed that heat shock protein 90 (HSP90) may be a potential target of PPP. Surface plasmon resonance and immunoprecipitation assay validated that PPP directly targets HSP90 and disrupts the binding of HSP90 to AKT, thereby suppressing GC cell proliferation. Thus, our study revealed that PPP may be a promising therapeutic compound for GC treatment.

A Combination of Ilizarov Frame, Externalized Locking Plate and Tibia Bridging for an Adult with Large Tibial Defect and Severe Varus Deformity Due to Chronic Osteomyelitis in Childhood: A Case Report.

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction-compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions.

Epidemiological Investigation of Pediatric Fractures-A Retrospective Cohort Study of 1129 Patients.

Background and Objectives: Fractures are common in pediatric trauma, and they are caused by a broad spectrum of factors. Only a few studies have discussed the mechanisms of injury and their relationships to different types of fractures. The most frequent type of fractures in different age groups remains unclear. Therefore, we aim to summarize the epidemiological characteristics of pediatric fractures in a medical center in Zhuhai, China from 2006 to 2021 and analyze the causes of fractures with the highest frequency in different age groups. Materials and Methods: We extracted the information from the Zhuhai Center for Maternal and Child Health Care of those under 14 years old who had fractures from 2006 to 2021. Results: We reviewed the information of 1145 children. The number of patients increased during the 15 years (p < 0.0001). The number of patients was significantly different between genders after Y2 (p = 0.014). In addition, more than two-thirds of patients (71.3%) had upper limb fractures, and all types of falls were the most common cause of fractures (83.6%). The incidence demonstrated an insignificant difference in age groups except for the fractures of humerus and radius. Moreover, we discovered that the prevalence of fall-related injuries decreased with age, while that of sports-related injuries increased with age. Conclusions: Our study demonstrates that the prevalence of fall-related injuries decreases with age, and that of sports-related injuries increases with age. Most patients have upper limb fractures, and all types of falls are the most common cause of fractures. Fracture types with the highest frequency differ in each age group. These findings might supplement current epidemiological knowledge of childhood fracture and provide references for decision-making in children's health policies.

Insights into the Mechanism of Metal-Catalyzed Transformation of Oxime Esters: Metal-Bound Radical Pathway vs Free Radical Pathway.

Controlling of radical reactivity by binding a radical to the metal center is an elegant strategy to overcome the challenge that radical intermediates are "too reactive to be selective". Yet, its application has seemingly been limited to a few strained-ring substrates, azide compounds, and diazo compounds. Meanwhile, first-row transition-metal-catalyzed (mainly, Fe, Ni, Cu) transformations of oxime esters have been reported recently in which the activation processes are assumed to follow free-radical mechanisms. In this work, we show by means of density functional theory calculations that the activation of oxime esters catalyzed by Fe(II) and Cu(I) catalysts more likely affords a metal-bound iminyl radical, rather than the presumed free iminyl radical, and the whole process follows a metal-bound radical mechanism. The as-formed metal-bound radical intermediates are an Fe(III)-iminyl radical (Stotal = 2, SFe = 5/2, and Siminyl = -1/2) and a Cu(II)-iminyl radical (Stotal = 0, SCu = 1/2, and Siminyl = -1/2). The discovery of such novel substrates affording metal-bound radical intermediates may facilitate the experimental design of metal-catalyzed asymmetric synthesis using oxime esters to achieve the desired enantioselectivity.

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Glenohumeral joint dislocation is rare in children with proximal humeral fractures: a descriptive study and literature review.

BACKGROUND: Glenohumeral dislocation combined with fracture of the proximal humerus is extremely rare in children, and this study aims to investigate its incidence in the pediatric population and review the treatment strategy for this condition. METHODS: Between Jan 2014 and Jan 2019, 280 patients with unilateral proximal humeral fractures were retrospectively reviewed. Imaging and follow-up notes were reviewed for patients with a predilection for glenohumeral joint dislocation. Six (2.14%) patients between the ages of 5 and 10 years were confirmed as glenohumeral joint dislocation and included in the study. All these patients underwent closed reduction and external fixation under general anesthesia. RESULTS: Out of 280 patients with proximal humeral fractures, only 6 patients, including 4 males and 2 females, were confirmed as glenohumeral joint dislocation. ROM was normal compared with the contralateral shoulder in every patient at the last follow-up. There was no case of radiological abnormality, including avascular necrosis or devascularization of the humeral head. CONCLUSIONS: Glenohumeral dislocation is a rare entity associated with the proximal humerus fracture in children, with an overall incidence in our case series was 2.14%. Reduction and stabilization of such injury using an external fixator is a suitable choice for pediatric patients that failed closed reduction.

Copper-Catalyzed Asymmetric Diyne Cyclization via [1,2]-Stevens-Type Rearrangement for the Synthesis of Chiral Chromeno[3,4-c]pyrroles.

Here, we report a copper-catalyzed asymmetric cascade cyclization/[1,2]-Stevens-type rearrangement via a non-diazo approach, leading to the practical and atom-economic assembly of various valuable chiral chromeno[3,4-c]pyrroles bearing a quaternary carbon stereocenter in generally moderate to good yields with wide substrate scope and excellent enantioselectivities (up to 99 % ee). Importantly, this protocol not only represents the first example of catalytic asymmetric [1,2]-Stevens-type rearrangement based on alkynes but also constitutes the first asymmetric formal carbene insertion into the Si-O bond.

Plating versus elastic stable intramedullary nailing for displaced pediatric midshaft clavicular fractures.

INTRODUCTION: Traditionally, operative treatment for displaced midshaft clavicle fractures in adolescents has been achieved by using a plate and screws. However, a minimally invasive trend has led surgeons to use the elastic stable intramedullary nail (ESIN) for displaced midshaft clavicle fractures. This study aims to compare the clinical outcomes of adolescent patients who were operated on with an ESIN vs. a plate. METHODS: All patients aged between 10 and 14 years with displaced midshaft clavicle fractures who were operated on at our institute between January 2014 and January 2018 were reviewed retrospectively. The preoperative data, including baseline information on the patients, and types of surgical procedure were collected from the hospital database. The postoperative data, including clinical outcome and complications, were collected during the follow-up visits. Clinical outcome was evaluated during outpatient visits using the American Shoulder and Elbow Surgeons (ASES) score. The scar problem was evaluated according to the Scar Cosmesis Assessment and Rating (SCAR) scale. RESULTS: A total of 73 patients were included. Patients were categorized into two groups: ESIN (n = 45; 27 males, 18 females) and plate (n = 28; 17 males, 11 females), according to surgical technique. The average age of the patients in the ESIN group was 12.2 ± 1.5 years, and that in the plate group was 12.2 ± 1.4 years. The ESIN group presented significantly less operative time (31.1 vs. 59.8 min), a shorter hospital stay (1.5 vs. 2.5 days), and a smaller incision (2.4 vs. 5.4 cm) as compared to the plate group (P < .001). The rate of scar concern was much higher in the plate group (71.4%) than the ESIN group (22.2%) (P < .001). There was no statistically significant difference in shoulder function between the ESIN group and the plate group at different time points. CONCLUSION: A conservative approach remains the first choice for a pediatric clavicle fracture. Both the ESIN and the plate are safe and effective treatment methods for displaced midshaft clavicle fractures in adolescents. The ESIN is superior to the plate given its shorter operative time, shorter hospital stay, lower rate of scar concern, and easier implant removal. LEVEL OF EVIDENCE: III, retrospective observational study.