Sweet regulation - The emerging immunoregulatory roles of hexoses.

BACKGROUND: It is widely acknowledged that dietary habits have profound impacts on human health and diseases. As the most important sweeteners and energy sources in human diets, hexoses take part in a broad range of physiopathological processes. In recent years, emerging evidence has uncovered the crucial roles of hexoses, such as glucose, fructose, mannose, and galactose, in controlling the differentiation or function of immune cells. AIM OF REVIEW: Herein, we reviewed the latest research progresses in the hexose-mediated modulation of immune responses, provided in-depth analyses of the underlying mechanisms, and discussed the unresolved issues in this field. KEY SCIENTIFIC CONCEPTS OF REVIEW: Owing to their immunoregulatory effects, hexoses affect the onset and progression of various types of immune disorders, including inflammatory diseases, autoimmune diseases, and tumor immune evasion. Thus, targeting hexose metabolism is becoming a promising strategy for reversing immune abnormalities in diseases.

Global research trends and hotspots of artificial intelligence research in spinal cord neural injury and restoration-a bibliometrics and visualization analysis.

Background: Artificial intelligence (AI) technology has made breakthroughs in spinal cord neural injury and restoration in recent years. It has a positive impact on clinical treatment. This study explores AI research's progress and hotspots in spinal cord neural injury and restoration. It also analyzes research shortcomings related to this area and proposes potential solutions. Methods: We used CiteSpace 6.1.R6 and VOSviewer 1.6.19 to research WOS articles on AI research in spinal cord neural injury and restoration. Results: A total of 1,502 articles were screened, in which the United States dominated; Kadone, Hideki (13 articles, University of Tsukuba, JAPAN) was the author with the highest number of publications; ARCH PHYS MED REHAB (IF = 4.3) was the most cited journal, and topics included molecular biology, immunology, neurology, sports, among other related areas. Conclusion: We pinpointed three research hotspots for AI research in spinal cord neural injury and restoration: (1) intelligent robots and limb exoskeletons to assist rehabilitation training; (2) brain-computer interfaces; and (3) neuromodulation and noninvasive electrical stimulation. In addition, many new hotspots were discussed: (1) starting with image segmentation models based on convolutional neural networks; (2) the use of AI to fabricate polymeric biomaterials to provide the microenvironment required for neural stem cell-derived neural network tissues; (3) AI survival prediction tools, and transcription factor regulatory networks in the field of genetics were discussed. Although AI research in spinal cord neural injury and restoration has many benefits, the technology has several limitations (data and ethical issues). The data-gathering problem should be addressed in future research, which requires a significant sample of quality clinical data to build valid AI models. At the same time, research on genomics and other mechanisms in this field is fragile. In the future, machine learning techniques, such as AI survival prediction tools and transcription factor regulatory networks, can be utilized for studies related to the up-regulation of regeneration-related genes and the production of structural proteins for axonal growth.

Dendritic copper oxide catalyst engineering weak-polarity Cu-O bond for high-efficiency nitrate electroreduction.

Nitrate reduction reaction (NO3RR) is deemed a promising pathway for both ammonia synthesis and water purification. Developing a high-efficiency catalyst with excellent NH3 selectivity and catalytic stability is desirable but remains challenging. In this work, a dendritic copper oxide catalyst (Cu-B2) has been developed to efficiently catalyze NO3RR for ammonia production, the Cu-B2 exhibits excellent catalytic performance, achieving an NH3 Faradaic efficiency as high as 94 % and an NH3 yield of 16.9 mg h-1 cm-2 with a current density of 192.3 mA cm-2 at - 0.6 V (vs. RHE, reversible hydrogen electrode). During NO3RR testing, the Cu-B2 catalysts are reduced in situ to form highly active Cu0/Cu+ sites, while retaining its dendritic morphology. Compared with other catalysts, the Cu-O bond in Cu-B2 catalyst has weaker polarity, resulting in Cu0/Cu+ sites in lower oxidation states. In situ attenuated total reflection surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) studies reveal the Cu-B2 catalyst exhibits a potential-independent capability for *NO3- adsorption and high conversion efficiency of NO2- intermediate into ammonia, DFT calculations reveal that Cu-B2 exhibts higher NO3- adsorption energy and lower NO3- adsorption energy barrier than Cu-B1, thus endowing it with a remarkably improved catalytic activity and durability.

[Endoscopic ultrasonography features of benign esophageal stenosis in children]. / å„¿ç«¥é£Ÿç®¡è‰¯æ€§ç‹­çª„çš„è¶ å£°å† é•œç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children. METHODS: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children. RESULTS: A total of 42 children with benign esophageal stenosis were included. Among these children, 19 (45%) had anastomotic stenosis after surgery for esophageal atresia, with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS, and had 0-12 sessions of endoscopic treatment (average 2.1 sessions); 5 children (12%) had corrosive esophageal stenosis and 1 child (2%) had physical esophageal stenosis, with unclear stratification of the esophageal walls on EUS, and they had 2-9 sessions of endoscopic treatment (average 5.3 sessions); 1 child (2%) had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology; 16 children (38%) had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS, among whom 6 received endoscopic treatment. During follow-up, 95% (40/42) of the children had significant alleviation of the symptoms such as vomiting and dysphagia. CONCLUSIONS: For benign esophageal stenosis in children, EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions, possible etiologies, and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications, thereby helping to optimize the treatment regimen.

Detection of Single Nucleotide Polymorphisms of Circulating Tumor DNA by Strand Displacement Amplification Coupled with Liquid Chromatography.

The detection of multiple single nucleotide polymorphisms (SNPs) of circulating tumor DNA (ctDNA) is still a great challenge. In this study, we designed enzyme-assisted nucleic acid strand displacement amplification combined with high-performance liquid chromatography (HPLC) for the simultaneous detection of three ctDNA SNPs. First, the trace ctDNA could be hybridized to the specially designed template strand, which initiated the strand displacement nucleic acid amplification process under the synergistic action of DNA polymerase and restriction endonuclease. Then, the targets would be replaced with G-quadruplex fluorescent probes with different tail lengths. Finally, the HPLC-fluorescence assay enabled the separation and quantification of multiple signals. Notably, this method can simultaneously detect both the wild type (WT) and mutant type (MT) of multiple ctDNA SNPs. Within a linear range of 0.1 fM-0.1 nM, the detection limits of BRAF V600E-WT, EGFR T790M-WT, and KRAS 134A-WT and BRAF V600E-MT, EGFR T790M-MT, and KRAS 134A-MT were 29, 31, and 11 aM and 22, 29, and 33 aM, respectively. By using this method, the mutation rates of multiple ctDNA SNPs in blood samples from patients with lung or breast cancer can be obtained in a simple way, providing a convenient and highly sensitive analytical assay for the early screening and monitoring of lung cancer.

Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing.

The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.

Spatio-temporal spread and evolution of Lassa virus in West Africa.

BACKGROUND: Lassa fever is a hemorrhagic disease caused by Lassa virus (LASV), which has been classified by the World Health Organization as one of the top infectious diseases requiring prioritized research. Previous studies have provided insights into the classification and geographic characteristics of LASV lineages. However, the factor of the distribution and evolution characteristics and phylodynamics of the virus was still limited. METHODS: To enhance comprehensive understanding of LASV, we employed phylogenetic analysis, reassortment and recombination detection, and variation evaluation utilizing publicly available viral genome sequences. RESULTS: The results showed the estimated the root of time of the most recent common ancestor (TMRCA) for large (L) segment was approximately 634 (95% HPD: [385879]), whereas the TMRCA for small (S) segment was around 1224 (95% HPD: [10301401]). LASV primarily spread from east to west in West Africa through two routes, and in route 2, the virus independently spread to surrounding countries through Liberia, resulting in a wider spread of LASV. From 1969 to 2018, the effective population size experienced two significant increased, indicating the enhanced genetic diversity of LASV. We also found the evolution rate of L segment was faster than S segment, further results showed zinc-binding protein had the fastest evolution rate. Reassortment events were detected in multiple lineages including sub-lineage IIg, while recombination events were observed within lineage V. Significant amino acid changes in the glycoprotein precursor of LASV were identified, demonstrating sequence diversity among lineages in LASV. CONCLUSION: This study comprehensively elucidated the transmission and evolution of LASV in West Africa, providing detailed insights into reassortment events, recombination events, and amino acid variations.

Macrophage: Hidden Criminal in Therapy Resistance.

BACKGROUND: Although substantial efforts have been made by researchers to develop drugs, a disappointing reality is that the emergence of drug resistance is an unavoidable reality for the majority of patients. In recent years, emerging evidence suggests a connection between drug resistance and immune dysregulation. SUMMARY: As a ubiquitously distributed, versatile innate immune cell, macrophages play essential roles in maintaining tissue homeostasis in a steady state. Nevertheless, it is becoming aware that macrophages undermine the action of therapeutic drugs across various disease types. Reprogramming macrophage function has been proven to be effective in restoring patient responsiveness to treatment. Herein, we comprehensively reviewed how macrophages respond to drugs and the mechanisms by which they contribute to treatment unresponsiveness in cancer, inflammatory diseases, and metabolic diseases. In addition, future prospects in macrophage-based combination therapy were discussed. KEY MESSAGES: Targeting macrophages is a promising strategy for overcoming drug resistance in immune disorders.

Willingness to receive the second booster of COVID-19 vaccine among older adults with cancer: a stratified analysis in four provinces of China.

Background: Despite the elevated COVID-19 risk for older adults with cancer, vaccine hesitancy poses a significant barrier to their immunization. Intriguingly, there is limited research on the prevalence of willingness to receive the second booster dose and associated determinants in older adults with cancer. Objective: Our objective was to ascertain the level of awareness about COVID-19 vaccines and to uncover the factors influencing the willingness to receive the second booster among Chinese cancer patients aged 65 years and over. Methods: To achieve our objective, we conducted a multicenter cross-sectional study in four tertiary hospitals from four provinces of China. This involved using a Health Belief Model (HBM) based self-administered questionnaire and medical records. Subsequently, we employed multivariable logistic regression to identify factors influencing the second COVID-19 booster vaccine willingness. Results: Our results showed that among 893 eligible participants, 279 (31.24%) were aged 65 years and over, and 614 (68.76%) were younger. Interestingly, the willingness to receive the second COVID-19 booster vaccine was 34.1% (95/279) (OR: 1.043, 95% CI: 0.858, 1.267) in participants aged 65 years and over, which was similar to participants aged under 65 years (34.1% vs. 35.5%, p = 0.673). Furthermore, our findings revealed that a positive attitude toward the booster and recommendations from healthcare providers and family members were positively associated with vaccine willingness. Conversely, perceptions of negative impacts on cancer control and vaccine accessibility regarding the second COVID-19 booster were inversely related to the outcome event (all p < 0.05). Conclusion: Our study concludes with the finding of a low willingness toward the second COVID-19 booster in Chinese cancer patients, particularly in the older adults, a fact which warrants attention. This reluctance raises their risk of infection and potential for severe outcomes. Consequently, we recommend using media and community outreach to dispel misconceptions, promote the booster's benefits, and encourage vaccine discussions with healthcare providers and family members.

RND1 inhibits epithelial-mesenchymal transition and temozolomide resistance of glioblastoma via AKT/GSK3-ß pathway.

GBM is one of the most malignant tumor in central nervous system. The resistance to temozolomide (TMZ) is inevitable in GBM and the characterization of TMZ resistance seriously hinders clinical treatment. It is worthwhile exploring the underlying mechanism of aggressive invasion and TMZ resistance in GBM treatment. Bioinformatic analysis was used to analyze the association between RND1 and a series of EMT-related genes. Colony formation assay and cell viability assay were used to assess the growth of U87 and U251 cells. The cell invasion status was evaluated based on transwell and wound-healing assays. Western blot was used to detect the protein expression in GBM cells. Treatment targeted RND1 combined with TMZ therapy was conducted in nude mice to evaluate the potential application of RND1 as a clinical target for GBM. The overexpression of RND1 suppressed the progression and migration of U87 and U251 cells. RND1 knockdown facilitated the growth and invasion of GBM cells. RND1 regulated the EMT of GBM cells via inhibiting the phosphorylation of AKT and GSK3-ß. The promoted effects of RND1 on TMZ sensitivity was identified both in vitro and in vivo. This research demonstrated that the overexpression of RND1 suppressed the migration and EMT status by downregulating AKT/GSK3-ß pathway in GBM. RND1 enhanced the TMZ sensitivity of GBM cells both in vitro and in vivo. Our findings may contribute to the targeted therapy for GBM and the understanding of mechanisms of TMZ resistance in GBM.

Mutations in BrABCG26, encoding an ATP-binding cassette transporter, are responsible for male sterility in Chinese cabbage (Brassica rapa L. ssp. pekinensis).

KEY MESSAGE: The gene BrABCG26 responsible for male sterility of Chinese cabbage was confirmed by two allelic mutants. Male-sterile lines are an important way of heterosis utilization in Chinese cabbage. In this study, two allelic male-sterile mutants msm3-1 and msm3-2 were obtained from a Chinese cabbage double haploid (DH) line 'FT' by using EMS-mutagenesis. Compared to the wild-type 'FT,' the stamens of mutants were completely degenerated and had no pollen, and other characters had no obvious differences. Cytological observation revealed that the failure of vacuolation of the mononuclear microspore, accompanied by abnormal tapetal degradation, resulted in anther abortion in mutants. Genetic analysis showed that a recessive gene controlled the mutant trait. MutMap combined with kompetitive allele specific PCR genotyping analyses showed that BraA01g038270.3C, encoding a transporter ABCG26 that played a vital role in pollen wall formation, was the candidate gene for msm3-1, named BrABCG26. Compared with wild-type 'FT,' the mutations existed on the second exon (C to T) and the sixth exon (C to T) of BrABCG26 gene in mutants msm3-1 and msm3-2, leading to the loss-of-function truncated protein, which verified the BrABCG26 function in stamen development. Subcellular localization and expression pattern analysis indicated that BrABCG26 was localized in the nucleus and was expressed in all organs, with the highest expression in flower buds. Compared to the wild-type 'FT,' the expressions of BrABCG26 were significantly reduced in flower buds and anthers of mutants. Promoter activity analysis showed that a strong GUS signal was detected in flower buds. These results indicated that BrABCG26 is responsible for the male sterility of msm3 mutants in Chinese cabbage.

Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.

Regulation of neurotransmitter release during presynaptic plasticity underlies varied forms of information processing in the brain. Munc13s play essential roles in release via their conserved C-terminal region, which contains a MUN domain involved SNARE complex assembly, and control multiple presynaptic plasticity processes. Munc13s also have a variable N-terminal region, which in Munc13-1 includes a calmodulin binding (CaMb) domain involved in short-term plasticity and a C2A domain that forms an inhibitory homodimer. The C2A domain is activated by forming a heterodimer with the zinc-finger domain of αRIMs, providing a link to αRIM-dependent short- and long-term plasticity. However, it is unknown how the functions of the N- and C-terminal regions are integrated, in part because of the difficulty of purifying Munc13-1 fragments containing both regions. We describe for the first time the purification of a Munc13-1 fragment spanning its entire sequence except for a flexible region between the C2A and CaMb domains. We show that this fragment is much less active than the Munc13-1 C-terminal region in liposome fusion assays and that its activity is strongly enhanced by the RIM2α zinc-finger domain together with calmodulin. NMR experiments show that the C2A and CaMb domains bind to the MUN domain and that these interactions are relieved by the RIM2α ZF domain and calmodulin, respectively. These results suggest a model whereby Munc13-1 activity in promoting SNARE complex assembly and neurotransmitter release are inhibited by interactions of the C2A and CaMb domains with the MUN domain that are relieved by αRIMs and calmodulin.

S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway.

Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells' interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target.

PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome.

The paraneoplastic Ma antigen (PNMA) proteins are associated with cancer-induced paraneoplastic syndromes that present with an autoimmune response and neurological symptoms. Why PNMA proteins are associated with this severe autoimmune disease is unclear. PNMA genes are predominantly expressed in the central nervous system and are ectopically expressed in some tumors. We show that PNMA2, which has been co-opted from a Ty3 retrotransposon, encodes a protein that is released from cells as non-enveloped virus-like capsids. Recombinant PNMA2 capsids injected into mice induce autoantibodies that preferentially bind external "spike" PNMA2 capsid epitopes, whereas a capsid-assembly-defective PNMA2 protein is not immunogenic. PNMA2 autoantibodies in cerebrospinal fluid of patients with anti-Ma2 paraneoplastic disease show similar preferential binding to spike capsid epitopes. PNMA2 capsid-injected mice develop learning and memory deficits. These observations suggest that PNMA2 capsids act as an extracellular antigen, capable of generating an autoimmune response that results in neurological deficits.

Clinical and Radiological Outcomes After Combined ACL and MPFL Reconstruction Versus Isolated ACL Reconstruction for ACL Injury With Patellar Instability.

BACKGROUND: An anterior cruciate ligament (ACL) injury accompanied by patellar instability (PI) is a topic that has gained orthopaedic surgeons' attention recently. Untreated PI is reportedly associated with worse clinical outcomes after isolated ACL reconstruction (ACLR) in patients after an ACL injury with PI. Nevertheless, the appropriate surgical approach and its long-term therapeutic effects in these patients remain unclear. PURPOSE: (1) To compare the clinical and radiological outcomes between isolated ACLR (iACLR) and combined ACLR and medial patellofemoral ligament reconstruction (cAMR) in patients after an ACL injury with PI and (2) to explore the correlations between these 2 procedures and clinical and radiological outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 106 patients diagnosed with an ACL injury accompanied by PI between January 2016 and April 2021 were analyzed in this study. There were 34 patients excluded because of missing postoperative radiological data. Among the remaining 72 patients, 34 patients underwent iACLR, while 38 patients underwent cAMR. Demographic characteristics, intraoperative findings, and patient-reported outcomes (Lysholm score, subjective International Knee Documentation Committee score, and Tegner activity score) were prospectively collected. Patellar alignment parameters and worsening patellofemoral osteoarthritis (PFOA) features (evaluated with the modified Whole-Organ Magnetic Resonance Imaging Score) were analyzed longitudinally on magnetic resonance imaging. The Kujala score was used to evaluate the functional recovery of the patellofemoral joint, and redislocations of the patella were prospectively recorded. Finally, multivariate logistic regression analysis was used to explore the correlations between these 2 procedures and clinical (not achieving the minimal detectable change [MDC] for the Lysholm score) and radiological (worsening PFOA features) outcomes. RESULTS: The mean follow-up duration was 28.9 ± 6.2 and 27.1 ± 6.8 months for the iACLR and cAMR groups, respectively (P = .231). Significantly higher Lysholm scores (88.3 ± 9.9 vs 82.1 ± 11.1, respectively; P = .016) and subjective International Knee Documentation Committee scores (83.6 ± 11.9 vs 78.3 ± 10.2, respectively; P = .046) were detected in the cAMR group compared with the iACLR group postoperatively. The rates of return to preinjury sports were 20.6% and 44.7% in the iACLR and cAMR groups, respectively (difference, 24.1% [95% CI, 3.3%-45.0%]; P = .030). Moreover, the rates of worsening PFOA features were 44.1% and 18.4% in the iACLR and cAMR groups, respectively (difference, 25.7% [95% CI, 4.9%-46.4%]; P = .018). In addition, significantly higher Kujala scores (87.9 ± 11.3 vs 80.1 ± 12.0, respectively; P = .006), lower redislocation rates (0.0% vs 11.8%, respectively; difference, 11.8% [95% CI, 0.9%-22.6%]; P = .045), and significantly better patellar alignment were detected in the cAMR group compared with the iACLR group postoperatively. Furthermore, multivariate logistic regression analysis determined that iACLR and partial lateral meniscectomy were significantly correlated with not achieving the MDC for the Lysholm score and worsening PFOA features in our study population. CONCLUSION: In patients after an ACL injury with PI, cAMR yielded better clinical and radiological outcomes compared with iACLR, with better patellar stability and a lower proportion of worsening PFOA features. Furthermore, not achieving the MDC for the Lysholm score and worsening PFOA features were significantly correlated with iACLR and partial lateral meniscectomy. Our study suggests that cAMR may be a more appropriate procedure for patients after an ACL injury with PI, which warrants further high-level clinical evidence.

Biomechanical Analysis Reveals Shoulder Instability With Bipolar Bone Loss Is Best Treated With Dynamic Anterior Stabilization for On-Track Lesions and with Remplissage for Off-Track Lesions.

PURPOSE: To compare the biomechanical effects of augmenting Bankart repair (BR) with either remplissage or dynamic anterior stabilization (DAS) in the treatment of anterior shoulder instability with on-track or off-track bipolar bone loss. METHODS: Eight fresh-frozen cadaveric shoulders were tested at 60° of glenohumeral abduction in the intact, injury, and repair conditions. Injury conditions included 15% glenoid bone loss with an on-track or off-track Hill-Sachs lesion as previously recommended. Repair conditions included isolated BR, BR with remplissage, and BR with DAS (long head of biceps transfer). The glenohumeral stability was assessed by measuring the anterior translation under 0, 10, 20, 30, 40, 50 N load and maximum load without causing instability at mid-range (60°) and end-range (90°) external rotation (ER). Maximum range of motion (ROM) was measured by applying a 2.2-N·m torque in passive ER and internal rotation. RESULTS: Isolated BR failed to restore native glenohumeral stability in both on-track and off-track bipolar bone loss models. Both remplissage and DAS significantly decreased the anterior instability in the bipolar bone loss models, showing better restoration than the isolated BR. In the on-track lesions, DAS successfully restored native glenohumeral stability and mobility, whereas remplissage significantly decreased anterior translation without load (-2.12 ± 1.07 mm at 90° ER, P = .003; -1.98 ± 1.23 mm at 60° ER, P = .015). In the off-track lesions, remplissage restored native glenohumeral stability but led to significant ROM limitation (-8.6° ± 2.3° for internal rotation, P < .001; -13.9° ± 6.2° for ER, P = .003), whereas DAS failed to restore native stability at 90° ER regarding the increased anterior translation under 50 N (4.10 ± 1.53 mm, P < .001) and decreased maximum load (-13.8 ± 9.2 N, P = .021). CONCLUSIONS: At time-zero, both remplissage and DAS significantly reduced residual anterior instability compared with isolated BR in the bipolar bone loss models and restored the native glenohumeral stability under most translational loads. However, remplissage could decrease the anterior translation without load for on-track lesions and may restrict ROM for off-track lesions, whereas DAS failed to restore native stability under high translational loads for off-track lesions. CLINICAL RELEVANCE: DAS could be recommended to treat on-track bipolar bone loss with less biomechanical adverse effects, whereas remplissage might be the preferred procedure to address off-track bipolar bone loss for better stability.

Cardiac lipidomic profiles in mice undergo changes from fetus to adult.

AIMS: Lipids are essential cellular components with many important biological functions. Disturbed lipid biosynthesis and metabolism has been shown to cause cardiac developmental abnormality and cardiovascular diseases. In this study, we aimed to investigate the composition and the molecular profiles of lipids in mammalian hearts between embryonic and adult stages and uncover the underlying links between lipid and cardiac development and maturation. MATERIALS AND METHODS: We collected mouse hearts at the embryonic day 11.5 (E11.5), E15.5, and the age of 2 months, 4 months and 10 months, and performed lipidomic analysis to determine the changes of the composition, molecular species, and relative abundance of cardiac lipids between embryonic and adult stages. Additionally, we also performed the electronic microscopy and RNA sequencing in both embryonic and adult mouse hearts. KEY FINDINGS: The relative abundances of certain phospholipids and sphingolipids including cardiolipin, phosphatidylglycerol, phosphatidylethanolamine, and ceramide, are different between embryonic and adult hearts. Such lipidomic changes are accompanied with increased densities of mitochondrial membranes and elevated expression of genes related to mitochondrial formation in adult mouse hearts. We also analyzed individual molecular species of phospholipids and sphingolipids, and revealed that the composition and distribution of lipid molecular species in hearts also change with development. SIGNIFICANCE: Our study provides not only a lipidomic view of mammalian hearts when developing from the embryonic to the adult stage, but also a potential pool of lipid indicators for cardiac cell development and maturation.

Control of Munc13-1 Activity by Autoinhibitory Interactions Involving the Variable N-terminal Region.

Regulation of neurotransmitter release during presynaptic plasticity underlies varied forms of information processing in the brain. Munc13s play essential roles in release via their conserved C-terminal region, which contains a MUN domain involved in SNARE complex assembly, and controls multiple presynaptic plasticity processes. Munc13s also have a variable N-terminal region, which in Munc13-1 includes a calmodulin binding (CaMb) domain involved in short-term plasticity and a C2A domain that forms an inhibitory homodimer. The C2A domain is activated by forming a heterodimer with the zinc-finger domain of αRIMs, providing a link to αRIM-dependent short- and long-term plasticity. However, it is unknown how the functions of the N- and C-terminal regions are integrated, in part because of the difficulty of purifying Munc13-1 fragments containing both regions. We describe for the first time the purification of a Munc13-1 fragment spanning its entire sequence except for a flexible region between the C2A and CaMb domains. We show that this fragment is much less active than the Munc13-1 C-terminal region in liposome fusion assays and that its activity is strongly enhanced by the RIM2α zinc-finger domain together with calmodulin. NMR experiments show that the C2A and CaMb domains bind to the MUN domain and that these interactions are relieved by the RIM2α ZF domain and calmodulin, respectively. These results suggest a model whereby Munc13-1 activity in promoting SNARE complex assembly and neurotransmitter release are inhibited by interactions of the C2A and CaMb domains with the MUN domain that are relieved by αRIMs and calmodulin.

Low uptake of COVID-19 booster doses among elderly cancer patients in China: A multicentre cross-sectional study.

Background: Vaccination is a crucial measure to control the spread of coronavirus disease 2019 (COVID-19) pandemic. The elderly and cancer populations both are more susceptible to SARS-CoV-2 and have higher mortality. However, the uptake of COVID-19 vaccine booster doses among elderly cancer patients remains unclear. This study aimed to investigate the prevalence and associates of COVID-19 vaccine booster doses uptake in elderly cancer patients. Methods: A multi-center cross-sectional survey was conducted in four general populations of China province from April to June 2022. Demographic and clinical characteristics, as well as COVID-19 vaccination status and reasons for not uptake booster doses, were collected through face-to-face interviews and medical records. Multivariable logistic regression models were performed to explore the associates of the first COVID-19 booster dose vaccination uptake of cancer patients. Results: A total of 893 cancer patients were eventually included in this study, of which 279 (31.24%) were aged 65 or older and 614 (68.76%) were under 65 years old. The proportion of the first COVID-19 vaccine booster dose among cancer patients aged 65 and above was lower than among adults aged 65 (23.66 vs. 31.92%). Factors affecting individual-level variables among the aged 65 and above cancer patients group whether to uptake the first COVID-19 booster dose were negative attitudes toward COVID-19 vaccine booster dose, perceived subjective norm, perceived behavioural control, and other types of chronic disease. There is no significant difference in the incidence of related adverse reactions between the two age groups (P = 0.19). Conclusions: Low uptake of COVID-19 vaccine booster doses among elderly cancer patients is a significant concern and implies high susceptibility and high fatality when facing the emergence of SARS Cov-2 outbreak. Efforts to improve vaccine education and accessibility, particularly in rural areas, may help increase uptake and reduce the spread of SARS-Cov-2.