STING regulates aging-related osteoporosis by mediating the Hk2-Vdac1 mitochondrial axis.

Metabolic abnormalities and mild inflammation are hallmarks of aging and major driving factors for aging-related damage and bone metabolic diseases. Mitochondria are crucial links in energy metabolism and immune homeostasis regulation. Mitochondrial dysfunction is considered one of the pathogenic factors of aging-related osteoporosis, but its mechanism of action needs further research. Here, we demonstrated that the interaction between stimulator of interferon genes (STING)-mediated regulation of hexokinase 2 (Hk2)-voltage-dependent anion channel-1 (Vdac1) is a critical factor contributing to mitochondrial dysfunction and osteogenic abnormalities during aging. As the aging process progresses, factors related to aging cause an increase in STING expression, which disrupts the interaction between Hk2 and Vdac1. Dissociation of Hk2 from Vadc1 triggered the opening of the mitochondrial inner mitochondrial permeability transition pore (mPTP), leading to mitochondrial dysfunction and abnormal osteogenic differentiation, thereby disrupting bone homeostasis. In brief, this study demonstrates that STING acts as an intracellular metabolic Checkpoint, influencing mitochondrial function to promote the development of osteoporosis. These findings significantly enhance the development of STING-targeted treatments for aging-related osteoporosis.

An Engineered Hierarchical Hydrogel with Immune Responsiveness and Targeted Mitochondrial Transfer to Augmented Bone Regeneration.

Coordinating the immune response and bioenergy metabolism in bone defect environments is essential for promoting bone regeneration. Mitochondria are important organelles that control internal balance and metabolism. Repairing dysfunctional mitochondria has been proposed as a therapeutic approach for disease intervention. Here, an engineered hierarchical hydrogel with immune responsiveness can adapt to the bone regeneration environment and mediate the targeted mitochondria transfer between cells. The continuous supply of mitochondria by macrophages can restore the mitochondrial bioenergy of bone marrow mesenchymal stem cells (BMSC). Fundamentally solving the problem of insufficient energy support of BMSCs caused by local inflammation during bone repair and regeneration. This discovery provides a new therapeutic strategy for promoting bone regeneration and repair, which has research value and practical application prospects in the treatment of various diseases caused by mitochondrial dysfunction.

Synaptic ring attractor: A unified framework for attractor dynamics and multiple cues integration.

Effective cue integration is essential for an animal's survival. The ring attractor network has emerged as a powerful framework for understanding how animals seamlessly integrate various cues. This network not only elucidates neural dynamics within the brain, especially in spatial encoding systems like the heading direction (HD) system, but also sheds light on cue integration within decision-making processes. Yet, many significant phenomena across different fields lack clear explanations. For instance, in physiology, the integration mechanism of Drosophila's compass neuron when confronted with conflicting self-motion cues and external sensory cues with varying gain control settings is not well elucidated. Similarly, in ethology, the decision-making system shows Bayesian integration (BI) under minimal cue conflicts, but shifts to a winner-take-all (WTA) mode as conflicts surpass a certain threshold. To address these gaps, we introduce a ring attractor network with asymmetrical neural connections and synaptic dynamics in this paper. A thorough series of simulations has been conducted to assess its ability to track external cues and integrate conflicting cues. The results from these simulations demonstrate that the proposed model replicates observed neural dynamics and offers a framework for modeling biologically plausible cue integration behaviors. Furthermore, our findings yield several testable predictions that could inform future neuroethological research, providing insights into the role of ring attractor dynamics in the animal brain.

Enhanced ICD-10 code assignment of clinical texts: A summarization-based approach.

BACKGROUND: Assigning International Classification of Diseases (ICD) codes to clinical texts is a common and crucial practice in patient classification, hospital management, and further statistics analysis. Current auto-coding methods mainly transfer this task to a multi-label classification problem. Such solutions are suffering from high-dimensional mapping space and excessive redundant information in long clinical texts. To alleviate such a situation, we introduce text summarization methods to the ICD coding regime and apply text matching to select ICD codes. METHOD: We focus on the tenth revision of the ICD (ICD-10) coding and design a novel summarization-based approach (SuM) with an end-to-end strategy to efficiently assign ICD-10 code to clinical texts. In this approach, a knowledge-guided pointer network is purposed to distill and summarize key information in clinical texts precisely. Then a matching model with matching-aggregation architecture follows to align the summary result with code, tuning the one-vs-all scenario to one-vs-one matching so that the large-label-space obstacle laid in classification approaches would be avoided. RESULT: The 12,788 ICD-10 coded discharge summaries from a Chinese hospital were collected to evaluate the proposed approach. Compared with existing methods, the purposed model achieves the greatest coding results with Micro AUC of 0.9548, MRR@10 of 0.7977, Precision@10 of 0.0944, and Recall@10 of 0.9439 for the TOP-50 Dataset. Results on the FULL-Dataset remain consistent. Also, the proposed knowledge encoder and applied end-to-end strategy are proven to facilitate the whole model to gain efficacy in selecting the most suitable code. CONCLUSION: The proposed automatic ICD-10 code assignment approach via text summarization can effectively capture critical messages in long clinical texts and improve the performance of ICD-10 coding of clinical texts.

Identification of In Vivo Internalizing Cardiac-Specific RNA Aptamers.

Background: The pursuit of selective therapeutic delivery to target tissue types represents a key goal in the treatment of a range of adverse health issues, including diseases afflicting the heart. The development of new cardiac-specific ligands is a crucial step towards effectively targeting therapeutics to the heart. Methods: Utilizing an ex vivo and in vivo SELEX approaches, we enriched a library of 2'-fluoro modified aptamers for ventricular cardiomyocyte specificity. Lead candidates were identified from this library, and their binding and internalization into cardiomyocytes was evaluated in both ex vivo and in vivo mouse studies. Results: The ex vivo and in vivo SELEX processes generated an aptamer library with significant cardiac specificity over non-cardiac tissues such as liver and skeletal muscle. Our lead candidate aptamer from this library, CA1, demonstrates selective in vivo targeting and delivery of a fluorophore cargo to ventricular cardiomyocytes within the murine heart, while minimizing off-target localization to non-cardiac tissues, including the liver. By employing a novel RNase-based assay to evaluate aptamer interactions with cardiomyocytes, we discovered that CA1 predominantly internalizes into ventricular cardiomyocytes; conversely, another candidate CA41 primarily binds to the cardiomyocyte cell surface. Conclusions: These findings suggest that CA1 and CA41 have the potential to be promising candidates for targeted drug delivery and imaging applications in cardiac diseases.

Safety, Immunogenicity, and Effectiveness of Chinese-Made COVID-19 Vaccines in the Real World: An Interim Report of a Living Systematic Review.

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute's Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines' effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2-82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8-4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.

NFIC mediates m6A mRNA methylation to orchestrate transcriptional and post-transcriptional regulation to represses malignant phenotype of non-small cell lung cancer cells.

BACKGROUND: Multiple genetic and epigenetic regulatory mechanisms are crucial in the development and tumorigenesis process. Transcriptional regulation often involves intricate relationships and networks with post-transcriptional regulatory molecules, impacting the spatial and temporal expression of genes. However, the synergistic relationship between transcription factors and N6-methyladenosine (m6A) modification in regulating gene expression, as well as their influence on the mechanisms underlying the occurrence and progression of non-small cell lung cancer (NSCLC), requires further investigation. The present study aimed to investigate the synergistic relationship between transcription factors and m6A modification on NSCLC. METHODS: The transcription factor NFIC and its potential genes was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). The association of NFIC and its potential target genes were validated through ChIP-qPCR and dual-luciferase reporter assays. Additionally, the roles of NFIC and its potential genes in NSCLC were detected in vitro and in vivo through silencing and overexpression assays. RESULTS: Based on multi-omics data, the transcription factor NFIC was identified as a potential tumor suppressor of NSCLC. NFIC was significantly downregulated in both NSCLC tissues and cells, and when NFIC was overexpressed, the malignant phenotype and total m6A content of NSCLC cells was suppressed, while the PI3K/AKT pathway was inactivated. Additionally, we discovered that NFIC inhibits the expression of METTL3 by directly binding to its promoter region, and METTL3 regulates the expression of KAT2A, a histone acetyltransferase, by methylating the m6A site in the 3'UTR of KAT2A mRNA in NSCLC cells. Intriguingly, NFIC was also found to negatively regulate the expression of KAT2A by directly binding to its promoter region. CONCLUSIONS: Our findings demonstrated that NFIC suppresses the malignant phenotype of NSCLC cells by regulating gene expression at both the transcriptional and post-transcriptional levels. A deeper comprehension of the genetic and epigenetic regulatory mechanisms in tumorigenesis would be beneficial for the development of personalized treatment strategies.

Electron-Induced Nonmonotonic Pressure Dependence of the Lattice Thermal Conductivity of θ-TaN.

Recent theoretical and experimental research suggests that θ-TaN is a semimetal with high thermal conductivity (κ), primarily due to the contribution of phonons (κ_{ph}). By using first-principles calculations, we show a nonmonotonic pressure dependence of the κ of θ-TaN. κ_{ph} first increases until it reaches a maximum at around 60 GPa, and then decreases. This anomalous behavior is a consequence of the competing pressure responses of phonon-phonon and phonon-electron interactions, in contrast to the known materials BAs and BP, where the nonmonotonic pressure dependence is caused by the interplay between different phonon-phonon scattering channels. Although TaN has phonon dispersion features similar to BAs at ambient pressure, its response to pressure is different and an overall stiffening of the phonon branches takes place. Consequently, the relevant phonon-phonon scattering weakens as pressure increases. However, the increased electronic density of states near the Fermi level, and specifically the emergence of additional pockets of the Fermi surface at the high-symmetry L point in the Brillouin zone, leads to a substantial increase in phonon-electron scattering at high pressures, driving a decrease in κ_{ph}. At intermediate pressures (∼20-70 GPa), the κ of TaN surpasses that of BAs. Our Letter provides deeper insight into phonon transport in semimetals and metals where phonon-electron scattering is relevant.

Effect of corneal cross-linking on biomechanical changes following transepithelial photorefractive keratectomy and femtosecond laser-assisted LASIK.

Purpose: To evaluate the change in corneal biomechanics in patients with postoperative ectasia risk when combining two common laser vision correction procedures (tPRK and FS-LASIK) with cross-linking (in tPRK Xtra and FS-LASIK Xtra). Methods: The study included 143 eyes of 143 myopic, astigmatic patients that were divided into non-cross-linked refractive surgery groups (non-Xtra groups, tPRK and FS-LASIK) and cross-linked groups (Xtra groups, tPRK Xtra and FS-LASIK Xtra) according to an ectasia risk scoring system. The eyes were subjected to measurements including the stress-strain index (SSI), the stiffness parameter at first applanation (SP-A1), the integrated inverse radius (IIR), the deformation amplitude at apex (DA), and the ratio of deformation amplitude between apex and 2 mm from apex (DARatio2mm). The measurements were taken preoperatively and at 1, 3, and 6 months postoperatively (pos1m, pos3m, and pos6m). Posterior demarcation line depth from the endothelium (PDLD) and from the ablation surface (DLA) were recorded at pos1m. Results: SP-A1 significantly decreased, while IIR, deformation amplitude, and DARatio2mm increased significantly postoperatively in all four groups (p < 0.01)-all denoting stiffness decreases. In the FS-LASIK group, the changes in IIR, DA, and DARatio2mm were 32.7 ± 15.1%, 12.9 ± 7.1%, and 27.2 ± 12.0% respectively, which were significantly higher (p < 0.05) compared to 20.1 ± 12.8%, 6.4 ± 8.2%, and 19.7 ± 10.4% in the FS-LASIK Xtra group. In the tPRK group, the change in IIR was 27.3 ± 15.5%, significantly larger than 16.9 ± 13.4% in the tPRK Xtra group. The changes of SSI were minimal in the tPRK (-1.5 ± 21.7%, p = 1.000), tPRK Xtra (8.4 ± 17.9%, p = 0.053), and FS-LASIK Xtra (5.6 ± 12.7%, p = 0.634) groups, but was significant in the FS-LASIK group (-12.1 ± 7.9%, p < 0.01). After correcting for baseline biomechanical metrics, preoperative bIOP and the change in central corneal thickness (△CCT) from pre to pos6m, the changes in the IIR in both FS-LASIK and tPRK groups, as well as DA, DARatio2mm and SSI in the FS-LASIK group remained statistically greater than their corresponding Xtra groups (all p < 0.05). Most importantly, after correcting for these covariates, the changes in DARatio2mm in the FS-LASIK Xtra became statistically smaller than in the tPRK Xtra (p = 0.017). Conclusion: The statistical analysis results indicate that tPRK Xtra and FS-LASIK Xtra effectively reduced the biomechanical losses caused by refractive surgery (tPRK and FS-LASIK). The decrease in corneal overall stiffness was greater in FS-LASIK than in tPRK, and the biomechanical enhancement of CXL was also higher following LASIK than after tPRK.

C-reactive protein/lymphocyte ratio as a prognostic biomarker in acute pancreatitis: a cross-sectional study assessing disease severity.

BACKGROUND: The C-reactive protein/lymphocyte ratio (CLR) is a prognostic biomarker of various diseases. However, its significance in acute pancreatitis (AP) remains unknown. The main aim of this study was to investigate the association between the CLR and disease severity in patients with AP. METHODS: This cross-sectional study included 476 AP patients [mild acute pancreatitis (MAP), n =176; moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP), n =300]. The primary exposure of interest was the baseline CLR. The primary outcome was the incidence of moderate to severe AP. Multivariate logistic regression and restricted cubic spline analyses were performed to evaluate the association between the CLR and the incidence of moderate to severe AP. Receiver operating characteristic (ROC) analysis was conducted to assess the predictive efficacy, sensitivity, and specificity of CLR in predicting the incidence of moderate to severe AP. RESULTS: The mean age of the patients was 44±13.2 years, and 76.5% were male. The distribution of CLR was 31.6 (interquartile range, 4.5, 101.7). Moderate to severe AP occurred in 300 cases (63.0%). After multiple adjustments, CLR was independently associated with the incidence of moderate to severe AP (odds ratio, 1.04; 95% CI: 1.03-1.05; P < 0.001). A nonlinear relationship was found between CLR and the incidence of moderate to severe AP, with a threshold of approximately 45. The effect size and CI below and above the threshold value were 1.061 (1.033-1.089) and 1.014 (0.997-1.031), respectively. The area under the curve (AUC) for CLR was 87.577% (95% CI: 84.443- 90.710%) with an optimal cut-off value of 30.835, resulting in a sensitivity of 73.7% and a specificity of 88.6%. CONCLUSIONS: There was a nonlinear relationship with a saturation effect between the CLR and the incidence of moderate to severe AP. The CLR measured within 24 h of admission may serve as a promising biomarker for predicting the emergence of moderate to severe AP, thereby providing a more scientifically grounded basis for preventing such cases. Nonetheless, further research is warranted to validate and strengthen these findings.

YY1-induced lncRNA00511 promotes melanoma progression via the miR-150-5p/ADAM19 axis.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) are therapeutic targets and key regulators of tumors development and progression, including melanoma. Long intergenic non-protein-coding RNA 511 (LINC00511) has been demonstrated as an oncogenic molecule in breast, stomach, colorectal, and lung cancers. However, the precise role and functional mechanisms of LINC00511 in melanoma remain unknown. This study confirmed that LINC00511 was highly expressed in melanoma cells (A375 and SK-Mel-28 cells) and tissues, knockdown of LINC00511 could inhibit melanoma cell migration and invasion, as well as the growth of subcutaneous tumor xenografts in vivo. By using Chromatin immunoprecipitation (ChIP) assay, it was demonstrated that the transcription factor Yin Yang 1 (YY1) is capable of binding to the LINC00511 promoter and enhancing its expression in cis. Further mechanistic investigation showed that LINC00511 was mainly enriched in the cytoplasm of melanoma cells and interacted directly with microRNA-150-5p (miR-150-5p). Consistently, the knockdown of miR-150-5p could recover the effects of LINC00511 knockdown on melanoma cells. Furthermore, ADAM metallopeptidase domain expression 19 (ADAM19) was identified as a downstream target of miR-150-5p, and overexpression of ADAM19 could promote melanoma cell proliferation. Rescue assays indicated that LINC00511 acted as a competing endogenous RNA (ceRNA) to sponge miR-150-5p and increase the expression of ADAM19, thereby activating the PI3K/AKT pathway. In summary, we identified LINC00511 as an oncogenic lncRNA in melanoma and defined the LINC00511/miR-150-5p/ADAM19 axis, which might be considered a potential therapeutic target and novel molecular mechanism the treatment of patients with melanoma.

Diagnostic and prognostic potential of exosome non-coding RNAs in bladder cancer: a systematic review and meta-analysis.

Background: Bladder cancer stands as the predominant malignant tumor in the urological system, presenting a significant challenge to public health and garnering extensive attention. Recently, with the deepening research into tumor molecular mechanisms, non-coding RNAs (ncRNAs) have emerged as potential biomarkers offering guidance for the diagnosis and prognosis of bladder cancer. However, the definitive role of ncRNAs in bladder cancer remains unclear. Hence, this study aims to elucidate the relevance and significance of ncRNAs through a Meta-analysis. Methods: A systematic meta-analysis was executed, including studies evaluating the diagnostic performance of ncRNAs and their associations with overall survival (OS) and disease-free survival (DFS). Key metrics such as hazard ratios, sensitivity, specificity, and diagnostic odds ratios were extracted and pooled from these studies. Potential publication bias was assessed using Deeks' funnel plot, and the robustness of the results was ascertained through a sensitivity analysis. Results: Elevated ncRNA expression showed a positive correlation with improved OS, evidenced by a hazard ratio (HR) of 0.82 (95% CI: 0.66-0.96, P<0.001). Similarly, a significant association was observed between heightened ncRNA expression and DFS, with an HR of 0.86 (95% CI: 0.73-0.99, P<0.001). Diagnostic performance analysis across 17 articles yielded a pooled sensitivity of 0.76 and a specificity of 0.83. The diagnostic odds ratio was recorded at 2.71, with the area under the ROC curve (AUC) standing at 0.85. Conclusion: Exosome ncRNAs appear to possess potential significance in the diagnostic and prognostic discussions of bladder cancer. Their relationship with survival outcomes and diagnostic measures suggests a possible clinical utility. Comprehensive investigations are needed to fully determine their role in the ever-evolving landscape of bladder cancer management, especially within the framework of personalized medicine.

A meta-analysis of the risk factors for surgical site infection in patients with colorectal cancer.

The purpose of the meta-analysis was to evaluate and compare the surgical site infection (SSI) risk factors in patients with colorectal cancer (CC). The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random or fixed-effect models. For the current meta-analysis, 23 examinations spanning from 2001 to 2023 were included, encompassing 89 859 cases of CC. Clean-contaminated surgical site wounds had significantly lower infections (OR, 0.36; 95% CI, 0.20-0.64, p < 0.001) compared to contaminated surgical site wounds in patients with CCs. Males had significantly higher SSIs (OR, 1.18; 95% CI, 1.12-1.24, p < 0.001) compared to females in patients with CC. American Society of Anesthesiology score ≥3 h had a significantly higher SSI (OR, 1.42; 95% CI, 1.18-1.71, p < 0.001) compared to <3 score in patients with CCs. Body mass index ≥25 had significantly higher SSIs (OR, 1.54; 95% CI, 1.11-2.14, p = 0.01) compared to <25 in patients with CCs. The presence of stoma creation had a significantly higher SSI rate (OR, 2.28; 95% CI, 1.37-3.79, p = 0.001) compared to its absence in patients with CC. Laparoscopic surgery had significantly lower SSIs (OR, 0.68; 95% CI, 0.59-0.78, p < 0.001) compared to open surgery in patients with CC. The presence of diabetes mellitus had a significantly higher SSI rate (OR, 1.24; 95% CI, 1.15-1.33, p < 0.001) compared to its absence in patients with CCs. No significant difference was found in SSI rate in patients with CCs between <3 and ≥3 h of operative time (OR, 1.07; 95% CI, 0.75-1.51, p = 0.72), between the presence and absence of blood transfusion (OR, 1.60; 95% CI, 0.69-3.66, p = 0.27) and between the presence and absence of previous laparotomies (OR, 1.47; 95% CI, 0.93-2.32, p = 0.10). The examined data revealed that contaminated wounds, male sex, an American Society of Anesthesiology score ≥3 h, a body mass index ≥25, stoma creation, open surgery and diabetes mellitus are all risk factors for SSIs in patients with CC. However, operative time, blood transfusion and previous laparotomies were not found to be risk factors for SSIs in patients with CC. However, given that several comparisons had a small number of chosen research, consideration should be given to their values.

Developing a highly efficient CGBE base editor in watermelon.

Cytosine and adenosine base editors (CBEs and ABEs) are novel genome-editing tools that have been widely utilized in molecular breeding to precisely modify single-nucleotide polymorphisms (SNPs) critical for plant agronomic traits and species evolution. However, conventional BE editors are limited to achieve C-to-T and A-to-G substitutions, respectively. To enhance the applicability of base editing technology in watermelon, we developed an efficient CGBE editor (SCGBE2.0) by removing the uracil glycosylase inhibitor (UGI) unit from the commonly used hA3A-CBE and incorporating the uracil-DNA glycosylase (UNG) component. Seven specific guide RNAs (sgRNAs) targeting five watermelon genes were designed to assess the editing efficiency of SCGBE. The results obtained from stably transformed watermelon plants demonstrated that SCGBE2.0 could efficiently induce C-to-G mutations at positions C5-C9 in 43.2% transgenic plants (with a maximum base conversion efficiency of 46.1%) and C-to-A mutation at position C4 in 23.5% transgenic plants (with a maximum base conversion efficiency of 45.9%). These findings highlight the capability of our integrated SCGBE2.0 editor to achieve C-to-G/A mutations in a site-preferred manner, thus providing an efficient base editing tool for precise base modification and site-directed saturated mutagenesis in watermelon.

Biomaterials derived from hard palate mucosa for tissue engineering and regenerative medicine.

Autologous materials have superior biosafety and are widely used in clinical practice. Due to its excellent trauma-healing ability, the hard palate mucosa (HPM) has become a hot spot for autologous donor area research. Multiple studies have conducted an in-depth analysis of the healing ability of the HPM at the cellular and molecular levels. In addition, the HPM has good maneuverability as a donor area for soft tissue grafts, and researchers have isolated various specific mesenchymal stem cells (MSCs) from HPM. Free soft tissue grafts obtained from the HPM have been widely used in the clinic and have played an essential role in dentistry, eyelid reconstruction, and the repair of other specific soft tissue defects. This article reviews the advantages of HPM as a donor area and its related mechanisms, classes of HPM-derived biomaterials, the current status of clinical applications, challenges, and future development directions.

Diversification of JAZ-MYC signaling function in immune metabolism.

Jasmonate (JA) re-programs metabolism to confer resistance to diverse environmental threats. Jasmonate stimulates the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins that repress the activity of MYC transcription factors. In Arabidopsis thaliana, MYC and JAZ are encoded by 4 and 13 genes, respectively. The extent to which expansion of the MYC and JAZ families has contributed to functional diversification of JA responses is not well understood. Here, we investigated the role of MYC and JAZ paralogs in controlling the production of defense compounds derived from aromatic amino acids (AAAs). Analysis of loss-of-function and dominant myc mutations identified MYC3 and MYC4 as the major regulators of JA-induced tryptophan metabolism. We developed a JAZ family-based, forward genetics approach to screen randomized jaz polymutants for allelic combinations that enhance tryptophan biosynthetic capacity. We found that mutants defective in all members (JAZ1/2/5/6) of JAZ group I over-accumulate AAA-derived defense compounds, constitutively express marker genes for the JA-ethylene branch of immunity and are more resistant to necrotrophic pathogens but not insect herbivores. In defining JAZ and MYC paralogs that regulate the production of amino-acid-derived defense compounds, our results provide insight into the specificity of JA signaling in immunity.

Automatic ICD-10 coding: Deep semantic matching based on analogical reasoning.

Background: ICD-10 has been widely used in statistical analysis of mortality rates and medical reimbursement. Automatic ICD-10 coding is desperately needed because manually assigning codes is expensive, time-consuming, and labor-intensive. Diagnoses described in medical records differ significantly from those used in ICD-10 classification, making it impossible for existing automatic coding techniques to perform well enough to support medical billing, resource allocation, and research requirements. Meanwhile, most of the current automatic coding approaches are oriented toward English ICD-10. This method for automatically assigning ICD-10 codes to diagnoses extracted from Chinese discharge records was provided in this paper. Method: First, BERT creates word representations of the two texts. Second, the context representation layer incorporates contextual information into the representation of each time step of the word representations using a bidirectional Long Short-Term Memory. Third, the matching layer compares each contextual embedding of the uncoded diagnosis record against a weighted version of all contextual character embeddings of the manually coded diagnosis record. The matching strategy is element-wise subtraction and element-wise multiplication and then through a neural network layer. Fourth, the matching vectors are combined using a one-layer convolutional neural network. A sigmoid is then used to output matching results. Results: To evaluate the proposed method, 1,003,558 manually coded primary diagnoses were gathered from the homepage of the discharge medical records. The experimental results showed that the proposed method outperformed popular deep semantic matching algorithms, such as DSSM, ConvNet, ESIM, and ABCNN, and demonstrated state-of-the-art results in a single text matching with an accuracy of 0.986, a precision of 0.979, a recall of 0.983, and an F1-score of 0.981. Conclusion: The automatic ICD-10 coding of Chinese diagnoses is successful when using the proposed deep semantic matching approach based on analogical reasoning.

NLRP12-expressing dendritic cells mediate both dissemination of infection and adaptive immune responses in visceral leishmaniasis.

The NLR protein NLRP12 contributes to innate immunity, but the mechanism remains elusive. Infection of Nlrp12 -/- or wild-type mice with Leishmania infantum led to aberrant parasite tropism. Parasites replicated to higher levels in livers of Nlrp12 -/- mice than in the livers of WT mice and failed to disseminate to spleens. Most retained liver parasites resided in dendritic cells (DCs), with correspondingly fewer infected DCs in spleens. Furthermore, Nlrp12 -/- DCs expressed lower CCR7 than WT DCs, failed to migrate toward CCL19 or CCL21 in chemotaxis assays, and migrated poorly to draining lymph nodes after sterile inflammation. Leishmania-infected Nlpr12 -/- DCs were significantly less effective at transporting parasites to lymph nodes than WT DCs. Consistently, adaptive immune responses were also impaired in infected Nlrp12 -/- mice. We hypothesize that Nlrp12-expressing DCs are required for efficient dissemination and immune clearance of L. infantum from the site of initial infection. This is at least partly due to the defective expression of CCR7.

Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.

Skeletal muscle regulation is responsible for voluntary muscular movement in vertebrates. The genes of two essential proteins, teneurins and latrophilins (LPHN), evolving in ancestors of multicellular animals form a ligand-receptor pair, and are now shown to be required for skeletal muscle function. Teneurins possess a bioactive peptide, termed the teneurin C-terminal associated peptide (TCAP) that interacts with the LPHNs to regulate skeletal muscle contractility strength and fatigue by an insulin-independent glucose importation mechanism in rats. CRISPR-based knockouts and siRNA-associated knockdowns of LPHN-1 and-3 in the C2C12 mouse skeletal cell line shows that TCAP stimulates an LPHN-dependent cytosolic Ca2+ signal transduction cascade to increase energy metabolism and enhance skeletal muscle function via increases in type-1 oxidative fiber formation and reduce the fatigue response. Thus, the teneurin/TCAP-LPHN system is presented as a novel mechanism that regulates the energy requirements and performance of skeletal muscle.