DDIT3 aggravates TMJOA cartilage degradation via Nrf2/HO-1/NLRP3-mediated autophagy.

OBJECTIVE: DNA damage-inducible transcript 3 (DDIT3), as a downstream transcription factor of endoplasmic reticulum stress, is reported to regulate chondrogenic differentiation under physiological and pathological state. However, the specific involvement of DDIT3 in the degradation of condylar cartilage of temporomandibular joint osteoarthritis (TMJOA) is unclarified. DESIGN: The expression patterns of DDIT3 in condylar cartilage from monosodium iodoacetate-induced TMJOA mice were examined to uncover the potential role of DDIT3 in TMJOA. The Ddit3 knockout (Ddit3-/-) mice and their wildtype littermates (Ddit3+/+) were used to clarify the effect of DDIT3 on cartilage degradation. Primary condylar chondrocytes and ATDC5 cells were applied to explore the mechanisms of DDIT3 on autophagy and extracellular matrix (ECM) degradation in chondrocytes. The autophagy inhibitor chloroquine (CQ) was used to determine the effect of DDIT3-inhibited autophagy in vivo. RESULTS: DDIT3 were highly expressed in condylar cartilage from TMJOA mice. Ddit3 knockout alleviated condylar cartilage degradation and subchondral bone loss, compared with their wildtype littermates. In vitro study demonstrated that DDIT3 exacerbated ECM degradation in chondrocytes induced by TNF-α through inhibiting autophagy. The intraperitoneal injection of CQ further confirmed that Ddit3 knockout alleviated cartilage degradation in TMJOA through activating autophagy in vivo. CONCLUSIONS: Our findings identified the crucial role of DDIT3-inhibited autophagy in condylar cartilage degradation during the development of TMJOA.

A 90-day subchronic exposure to heated tobacco product aerosol caused differences in intestinal inflammation and microbiome dysregulation in rats.

INTRODUCTION: Smoking is one of the most important predisposing factors of intestinal inflammatory diseases. Heated tobacco product (HTP) is a novel tobacco category that is claimed to deliver reduced chemicals to human those reported in combustible cigarette smoke (CS). However, the effect of HTP on intestine is still unknown. METHODS: In the framework of Organization for Economic Co-operation and Development guidelines 413 guidelines, Sprague-Dawley rats were exposed to HTP aerosol and CS for 13 weeks. The atmosphere was characterized and oxidative stress and inflammation of intestine were investigated after exposure. Furthermore, the faeces we performed with 16S sequencing and metabolomics analysis. RESULTS: HTP aerosol and CS led to obvious intestinal damage evidenced by increased intestinal pro-inflammatory cytokines and oxidative stress in male and female rats After HTP and CS exposure, the abundance that obviously changed were Lactobacillus and Turiciacter in male rats and Lactobacillus and Prevotella in female rats. HTP mainly induced the metabolism of amino acids and fatty acyls such as short-chain fatty acids and tryptophan, while CS involved into the main metabolism of bile acids, especially indole and derivatives. Although different metabolic pathways in the gut mediated by HTP and CS, both to inflammation and oxidative stress were ultimately induced. CONCLUSIONS: HTP aerosol and CS induced intestinal damage mediated by different gut microbiota and metabolites, while both lead to inflammation and oxidative stress. IMPLICATIONS: The concentration of various harmful components in heated tobacco product aerosol is reported lower than that of traditional cigarette smoke, however, its health risk impact on consumers remains to be studied. Our research findings indicate that heated tobacco product and cigarette smoke inhalation induced intestinal damage through different metabolic pathways mediated by gut microbiome, indicating the health risk of heated tobacco product in intestine.

A novel microbial community restructuring strategy for enhanced hydrogen production using multiple pretreatments and CSTR operation.

To achieve rapid enrichment of the targeted hydrogen-producing bacterial population and reconstruction of the microbial community in the biological hydrogen-producing reactor, the activated sludge underwent multiple pretreatments using micro-aeration, alkaline treatment, and heat treatment. The activated sludge obtained from the multiple pretreatments was inoculated into the continuous stirred tank reactor (CSTR) for continuous operations. The community structure alteration and hydrogen-producing capability of the activated sludge were analyzed throughout the operation of the reactor. We found that the primary phyla in the activated sludge population shifted to Proteobacteria, Firmicutes, and Bacteroidetes, which collectively accounted for 96.69% after undergoing several pretreatments. This suggests that the multiple pretreatments facilitated in achieving the selective enrichment of the fermentation hydrogen-producing microorganisms in the activated sludge. The CSTR start-up and continuous operation of the biological hydrogen production reactor resulted in the reactor entering a highly efficient hydrogen production stage at influent COD concentrations of 4000 mg/L and 5000 mg/L, with the highest hydrogen production rate reaching 8.19 L/d and 9.33 L/d, respectively. The main genus present during the efficient hydrogen production stage in the reactor was Ethanoligenens, accounting for up to 33% of the total population. Ethanoligenens exhibited autoaggregation capabilities and a superior capacity for hydrogen production, leading to its prevalence in the reactor and contribution to efficient hydrogen production. During high-efficiency hydrogen production, flora associated with hydrogen production exhibited up to 46.95% total relative abundance. In addition, redundancy analysis (RDA) indicated that effluent pH and COD influenced the distribution of the primary hydrogen-producing bacteria, including Ethanoligenens, Raoultella, and Pectinatus, as well as other low abundant hydrogen-producing bacteria in the activated sludge. The data indicates that the multiple pretreatments and reactor's operation has successfully enriched the hydrogen-producing genera and changed the community structure of microbial hydrogen production.

Safety and efficacy of peripheral blood stem cells collection in healthy children and pediatric patients with thalassemia major weighing 20 kg or less.

BACKGROUND: Peripheral blood stem cell (PBSC) collection in children poses challenges due to their small size, low body weight (BW), and unique pediatric physiology, especially among children weighing 20 kg (kg) or less. METHODS: PBSC collection data of both healthy children and patients with thalassemia major (TM) weighing 20 kg or less between January 2013 and December 2020 were reviewed. Moreover, PBSCs characteristics along with various aspects of efficiency and safety between healthy donors and patients with TM were compared. RESULTS: A total of 262 PBSC procedures were performed on 255 children. Of these, 91 procedures were carried out on 85 allogeneic healthy donors, and 171 auto-backup collections were performed on 170 patients with TM to ensure PBSC availability and prevent transplantation failure. A minimum pre-apheresis hemoglobin (HGB) level of 60 g/L was discovered to be safe and feasible in patients with TM. The median CD34+ cell dose in the PBSC product during the initial apheresis procedure was higher in healthy donors compared to patients with TM (7.29 ± 5.28 × 106 cells/kg vs5.88 ± 4.23 × 106 cells/kg, P = .043). The total CD34+ cells/kg recipient weight exhibited a positive correlation with pre-apheresis monocyte counts, but a negative correlation with donor weight. Apheresis significantly reduced hematocrit and platelet counts in the allogeneic group compared to the autologous group. Patients with TM experienced a higher occurrence of bone pain related to granulocyte colony-stimulating factor treatment. Notably, no serious complications related to PBSCs mobilization, central venous catheter placement, or the apheresis procedure were observed in either group. CONCLUSIONS: PBSCs collection was both safe and effective in healthy children and pediatric patients with TM weighing 20 kg or less.

Unveiling the NIMBY effect in construction and demolition waste landfilling: Factors, paths, and solutions.

The construction and operation of the construction and demolition waste (C&DW) landfills often encounter significant opposition from nearby residents, which is called the "not in my backyard" (NIMBY) effect. However, little is known about the formation mechanism of the NIMBY effect in C&DW landfilling, so this research was conducted for this purpose. First, the influencing factors leading to the NIMBY effect were determined based on a literature review and questionnaire survey. Then, the interrelationship and influencing path of critical factors were revealed using expert interviews and Interpretative Structural Modelling. The results shown that 12 factors from four levels (including residents, society, government, and enterprises) caused the NIMBY effect in C&DW landfilling. These factors formed a complex network comprising 18 influencing paths. Notably, policy and responding measures as pivotal bottom-level factors that trigger the NIMBY effect by indirectly impacting residents' rights awareness and shaping public perception towards C&DW landfill operation enterprises through directly affecting personal interest, cognitive bias, distrust, disposal technology, management level, opinion leader, and other intermediate factors, ultimately triggering the NIMBY effect. Moreover, strategies for mitigating or resolving the NIMBY effect were proposed, such as protecting personal reasonable interests, understanding the potential risks of C&DW landfills rationally, reporting the C&DW landfills from an objective perspective, improving policies and promoting public participation, and enhancing supervision of the C&DW landfills. The study added new knowledge to the current public's NIMBY effect in C&DW landfilling. Meanwhile, it also provided a reference for formulating C&DW landfilling policies and selecting landfill sites.

Special issue "The advance of solid tumor research in China": Discoidin domain receptor 2 promotes colorectal cancer metastasis by regulating epithelial mesenchymal transition via activating AKT signaling.

Tumor metastasis is one of the main reasons for the high mortality rate associated with colorectal cancer (CRC). However, its underlying mechanisms have not been fully understood. Here, we reported that the expression of discoidin domain receptor 2 (DDR2) was significantly upregulated in CRC tissues compared to that in normal adjacent tissues. The expression level of DDR2 was negatively associated with prognosis of CRC patients. Therefore, DDR2 may play an oncogenic role in CRC development. Furthermore, DDR2 induced epithelial mesenchymal transition in CRC cells and regulated their invasive and metastatic capacity in vitro and in vivo. Mechanistically, increased DDR2 expression level activated the AKT/GSK-3ß/Slug signaling pathway. In conclusion, these findings showed that DDR2 promoted CRC metastasis and DDR2 inhibition might represent an effective therapeutic strategy for local advanced and metastatic CRC treatment.

A DNA Nano Firework for Imaging and Inhibitor Screening of Flap Endonuclease 1 in Living Cells.

In situ observation of changes in the activity of marker proteins in living cells is crucial for both biomarker-based disease diagnosis and drug screening. Flap endonuclease 1 (FEN1) has been recognized as a broad-spectrum cancer biomarker and therapeutic target. However, simple and reliable methods for in situ studying the FEN1 activity changes in living cells are limited. Here, we introduce a nano firework as a fluorescent sensor to sense and report FEN1 activity changes in living cells through FEN1 recognizing the substrates on the surface of the nano firework to release and restore the fluorescence of the prequenched fluorophores. We verified the high selectivity, anti-interference ability, stability, and quantitative performance of the nano firework in tubes and living cells, respectively. A series of controlled experiments have demonstrated that the nano firework could accurately report changes in FEN1 activity in different cells, enabling "sensors in, results out" in the manner of simple addition to the cell culture medium. Using an in silico molecular docking study and experiments, we also explored the ability of the nano firework for rapid screening of FEN1 inhibitors and found two new candidate compounds myricetrin and neoisoliquritin, which could be used as FEN1 inhibitors for further research. These performances of the nano firework suggest that it can be used in high-throughput screening applications, providing a promising tool for biomarker-based new drug discovery.

The chain mediating role of psychological resilience and neuroticism between intolerance of uncertainty and perceived stress among medical university students in Southwest China.

BACKGROUND: Medical university students are confronted with unprecedented uncertainty and stress compared with their peers. Research has explored the effect of intolerance of uncertainty on perceived stress, but little attention was paid to investigate the mediating mechanisms behind this relationship, especially among medical university students. The aim of this study was to examine whether psychological resilience and neuroticism played a mediating role between medical university students' intolerance of uncertainty and perceived stress. METHODS: A total of 717 medical university students from Chongqing in Southwest China were recruited to participate in our study and completed demographic information, Intolerance of Uncertainty Scale Short Version (IUS-12), Chinese Version of Perceived Stress Scale (CPSS), Connor-Davidson Resilience Scale-10 (CD-RISC-10) and Eysenck Personality Questionnaire (EPQ). RESULTS: (1) Significant correlations between intolerance of uncertainty, perceived stress, psychological resilience and neuroticism were found. (2) Intolerance of uncertainty affected medical university students' perceived stress via three paths: the mediating effect of psychological resilience, the mediating effect of neuroticism, and the chain mediating effect of both psychological resilience and neuroticism. CONCLUSIONS: Intolerance of uncertainty could directly affect the perceived stress of medical university students, and also affected perceived stress through the mediating roles of psychological resilience and neuroticism, as well as through the chain mediating role of these two variables.

Application of case-based learning in psychology teaching: a meta-analysis.

BACKGROUND: Case-based learning (CBL) has been found to be effective for many subjects, but there is currently a lack of evidence regarding its utility in psychology education. The present study investigated whether CBL pedagogy can improve students' academic performance in psychology courses compared to the traditional teaching methods. METHODS: A systematic review and meta-analysis were conducted to investigate the effectiveness of CBL in psychology teaching. Databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), the VIP database, and Wanfang data were searched to find eligible randomized controlled trials. Pooled effect estimates were calculated using Hedges' g under the random effects model, and a subgroup analysis was carried to investigate the heterogeneity among studies. RESULTS: Fifteen studies with 2172 participants, 1086 in the CBL group and 1086 in the traditional lecture-based teaching group, were included in the meta-analysis. Students in the CBL group scored significantly higher on exams than those in the lecture-based group [Hedges' g = 0.68, 95%CI (0.49, 0.88), p < 0.00]. Relatively high heterogeneity was noted among the included studies. Publication bias was examined by the funnel plot and Egger's test, but did not significantly influence the stability of the results. A subsequent evaluation using the trim-and-fill method confirmed that no single study was skewing the overall results. A qualitative review of the included studies suggested that most students in the CBL group were satisfied with the CBL teaching mode. CONCLUSIONS: This meta-analysis indicated that the CBL pedagogy could be effective in psychology education, and might help increase students' academic scores, while encouraging a more engaging and cooperative learning environment. At present, the application of CBL in psychology education is in its initial stage. Problems related to the curriculum itself, research methodology, and challenges faced by both teachers and learners have confined its practice. Fully tapping into the strengths of CBL in psychology teaching will require additional work and advancing research.

The relationship between sleep quality and depression: Critical roles of reflective and brooding rumination and sleep-related cognition.

There is a complex interplay between sleep problems and depression. This study explored the possible effects of rumination and dysfunctional beliefs about sleep on the relationship between sleep quality and depression. A cross-sectional survey of 1240 Chinese adults was conducted to assess the possible relationships. The results showed a chain mediating effect of reflection rumination and brooding rumination on the relationship between sleep quality and depression, accounting for 38.91% of the total variance. A moderating role of unreasonable attitudes about sleep was also discovered among the study participants, which enhanced the relationship between reflection and brooding, leading to a further increase in this relationship. Individually-tailored approaches targeting rumination and cognition may more effectively alleviate depression or co-morbid sleep problems and depression than the current standards of care.

DDR1 functions as an immune negative factor in colorectal cancer by regulating tumor-infiltrating T cells through IL-18.

Immunotherapies represented by programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have made great progress in the field of anticancer treatment, but most colorectal cancer patients do not benefit from immunotherapy. Discoidin domain receptor 1 (DDR1), a tyrosine kinase receptor, is activated by collagen binding and overexpressed in various malignancies. However, the role of DDR1 in colorectal cancer and immunoregulation remains unclear. In this study, we found DDR1 is highly expressed in colorectal cancer tissues and negatively associated with patient survival. We demonstrated that DDR1 promotes colorectal tumor growth only in vivo. Mechanistically, DDR1 is a negative immunomodulator in colorectal cancer and is involved in low infiltration of CD4+ and CD8+ T cells by inhibiting IL-18 synthesis. We also reported that DDR1 enhances the expression of PD-L1 through activating the c-Jun amino terminal kinase (JNK) signaling pathway. In conclusion, our findings elucidate the immunosuppressive role of DDR1 in colorectal cancer, which may represent a novel target to enhance the efficacy of immunotherapy in colorectal cancer.

FTO knockdown alleviates hypoxia-induced PC12 cell injury by stabilizing GADD45B in an IGF2BP2-dependent manner.

RNA N6-methyladenosine (m6A) level is closely associated with neurodevelopment and central nervous system dysfunctions including spinal cord injury (SCI). M6A level can be dynamically regulated by m6A methyltransferases and demethylases. In this text, the roles of m6A demethylase FTO alpha-ketoglutarate dependent dioxygenase (FTO) in SCI development along with its m6A-dependent regulatory mechanisms were investigated in hypoxia-induced PC12 cell injury model. The results showed that FTO was low expressed in spinal cord tissues of rats after contusive SCI and hypoxia-treated PC12 cells. FTO knockdown alleviated hypoxia-induced PC12 cell injury. FTO loss increased GADD45B expression and m6A level in PC12 cells. GADD45B knockdown weakened the protective effects of FTO depletion on hypoxia-treated PC12 cells. FTO regulated GADD45B expression in an IGF2BP2-dependent manner. In conclusion, FTO knockdown mitigated the injury of hypoxia-induced PC12 cells by up-regulating GADD45B in an IGF2BP2-dependent manner.

Electrosprayed Regeneration-Enhancer-Element Microspheres Power Osteogenesis and Angiogenesis Coupling.

Electrosprayed microspheres for bone regeneration are conventionally restricted by the lack of osteogenic modulation for both encapsulated stem cells and surrounding cells at the defect site. Here, sodium alginate microspheres encapsulating L-arginine doped hydroxyapatite nanoparticles (Arg/HA NPs) and bone mesenchymal stem cells (BMSCs) as regeneration-enhancer-element reservoirs (Arg/HA-SA@BMSC) for bone healing are electrosprayed. The Arg/HA NPs serve as a container of L-arginine and Ca2+ and the BMSCs inside the microspheres metabolize the released L-arginine into bioactive gas nitric oxide (NO) in the presence of Ca2+ to activate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Meanwhile, the generated NO diffuses out of the microspheres together with the Ca2+ and L-arginine as exterior enhancers to promote the osteogenesis-angiogenesis coupling of surrounding BMSCs and endothelial cells (ECs) at the bone defect site, generating an internal/external modulation loop between the encapsulated cells and surrounding native cells. It is demonstrated that such regeneration-enhancer-element reservoirs could effectively increase the bone tissue formation and neovasculature using rat calvarial defect models. It is envisioned that the microsphere system could streamline vascularized bone regeneration therapy as a high throughput, minimally invasive yet highly effective strategy to accelerate bone healing.

Giant axonal neuropathy (GAN) in an 8-year-old girl caused by a homozygous pathogenic splicing variant in GAN gene.

Giant axonal neuropathy (GAN) is a progressive disease that involves the peripheral and central nervous systems. This neurodegenerative disease is caused by variants in the GAN gene encoding gigaxonin, and is inherited in an autosomal recessive manner. Herein, we performed whole-exome sequencing on a 8-year-old child with dense, curly hair, weakness in both lower limbs, and abnormal MRI. The child was born to consanguineous parents. Our results revealed that the child carried the c.1373+1G>A homozygous pathogenic variant of the GAN gene, while both parents were heterozygous carriers. According to the validation at the cDNA levels, the splicing variant led to the skipping of exon 8 and affected the Kelch domain's formation. Unlike the previously reported cases of GAN, the child's clinical manifestations revealed peripheral nervous system involvement, no vertebral signs, cerebellar signs, and spasticity, but only MRI abnormalities. These results suggested that the patient's central nervous system was mildly involved, which may be related to the genotype. In order to further clarify the correlation between GAN genotype and phenotype, combined with this patient, 54 cases of reported homozygous variants of the GAN gene were merged for the analysis of genotype and phenotype. The results revealed a certain correlation between the GAN gene variant domain and the patient's clinical phenotype, such as central nervous system involvement and age of onset.

Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored. Here, we longitudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajectory. Moreover, re-analysis of a single cell study from CD8+ CD19 CAR-T confirmed our findings. These commonalities suggest conserved mechanisms for CAR-T treatment across hematological malignancies. Taken together, our current study provides insight into CAR-T cell dynamics during CAR-T therapy and proves that both BCMA CAR-T and CD19 CAR-T have similar transcriptional characteristics, especially at the CAR-T peak phase.

Ginsenoside Rb1 attenuates microglia activation to improve spinal cord injury via microRNA-130b-5p/TLR4/NF-κB axis.

Ginsenoside Rb1 (GRb1), a major ingredient of ginseng, has been found to be a potential protective agent in spinal cord injury (SCI) and in activated microglia-induced neuronal injury. This study discovered that GRb1 could facilitate miR-130b-5p expression in SCI rats and Toll-like receptor 4 (TLR4; a crucial player in inflammation) was a potential target of miR-130b-5p. Hence, we further investigated whether GRb1 could relieve SCI by reducing microglia-mediated inflammatory responses and neuronal injury via miR-130b-5p/TLR4 pathways. The results showed that GRb1 alleviated SCI through inhibiting neuronal apoptosis and proinflammatory factor expression via increasing miR-130b-5p.GRb1 weakened the damage of activated microglia to neurons through upregulating miR-130b-5p. miR-130b-5p attenuated activated microglia-induced neuron injury via targeting TLR4. GRb1 inactivated TLR4/nuclear factor-κB (NF-κB) activation and inhibited proinflammatory cytokine secretion by increasing miR-130b-5p in activated microglia. As a conclusion, GRb1 alleviated SCI through reducing activated microglia-induced neuronal injury via miR-130b-5p/TLR4/NF-κB axis, providing a deep insight into the molecular basis of GRb1 in the treatment of SCI.

Age-related alterations of default mode network in autobiographical memory: Recent versus remote events.

Previous studies have shown that the vividness of autobiographical memory decreases over time, and older adults often retrieve fewer details than young adults. However, the age-by-temporal distance (i.e., recent versus remote events) effect on autobiographical memory and underlying neural mechanisms are less understood. We recruited 25 young adults and 27 older adults to perform an fMRI-adapted autobiographical memory task with different temporal distances. The results showed that older adults' vividness ratings were generally higher than that of young adults, but were less sensitive to temporal distances. For neural imaging, an age-by-temporal distance effect was found in the left precuneus, manifested as young adults had more activation for recent events than for remote events, whereas no temporal distance effect was found in older adults. Interestingly, for older adults, the temporal distance effect was reflected by functional connectivity within the default mode network (DMN), with a stronger anterior DMN-posterior DMN coupling for remote events than for recent events, whereas no temporal distance difference on functional connectivity was found in young adults. The results suggest that older adults exhibit age-related neural differences in both activation and functional connectivity during the processing of autobiographical memory with different temporal distances, shedding new light for the understanding of the relationship between the DMN, autobiographical memory, and aging.

Effect of age of COVID-19 inpatient on the severity of the disease: A meta-analysis.

BACKGROUND: Clinical symptoms of adults and paediatric inpatients with COVID-19 disease are conflicting. This meta-analysis was conducted to assess the effect of age of COVID-19 inpatient on the severity of the disease. METHODS: A systematic literature search up to January 2021 was performed and 5 studies included 910 inpatients with COVID-19 disease at the baseline of the study; 773 of them were adult inpatients, and 137 of them were paediatric inpatients. They reported a comparison between adults and children with COVID-19 in the level of symptomatic severity, clinical features, computed tomography (CT) results and laboratory results. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated assessing the effect of age of COVID-19 inpatient on the severity of the disease using the dichotomous method with a random or fixed-effect model. RESULTS: Adults with COVID-19 disease had significantly lower number of mild cases (OR, 0.18; 95% CI, 0.04-0.77, P = .02); higher number severe cases (OR, 4.90; 95% CI, 2.03-11.83, P < .001); higher number of cases with fever (OR, 4.14; 95% CI, 2.31-7.43, P < .001); and higher number of cases with CT positive COVID-19 disease (OR, 2.04; 95% CI, 1.17-3.55, P = .001) compared with children. However, no significant difference was found between adults and children in number of cases with shortness of breath (OR, 1.44; 95% CI, 0.41-5.04, P = .57); dry cough (OR, 1.77; 95% CI, 0.64-4.93, P = .27); leukopenia (OR, 0.89; 95% CI, 0.47-1.66, P = .71); lymphopenia (OR, 0.96; 95% CI, 0.49-1.88, P = .91); high platelets (OR, 0.41; 95% CI, 0.17-1.02, P = .05); and high D-dimer (OR, 0.82; 95% CI, 0.43-1.56, P = .54). CONCLUSIONS: Adults with COVID-19 disease have a much higher level of symptomatic severity, fever and CT-positive COVID-19 disease than children. However, as shown in our results, the laboratory data were similar in both groups.

YAP1 inhibits the induction of TNF-α-stimulated bone-resorbing mediators by suppressing the NF-κB signaling pathway in MC3T3-E1 cells.

Yes-associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone-remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor-α (TNF-α) in MC3T3-E1 cells. The key osteoclastogenic molecules induced by TNF-α, namely, interleukin-6 and receptor activator of nuclear factor-κB (NF-κB) ligand, were suppressed after lentivirus-induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF-α-induced activation of the NF-κB signaling pathway as revealed by the reduced expression of phosphorylated-p65 and NF-κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF-α was reversed by berberine in concentration-dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption.

Autosomal dominant hereditary spastic paraplegia caused by mutation of UBAP1.

Hereditary spastic paraplegias (HSP) are a group of rare neurodegenerative diseases characterized by progressive spastic paraparesis. UBAP1 was recently found to induce a rare type of HSP (SPG80). We identified a family with eight inherited spastic paraplegic patients carrying a novel heterozygous mutation c.279delG (p.S94Vfs*9) of UBAP1. We demonstrated a lack of functional UBAP1 in these patients, resulting in the neurological disorder caused by interceptions of the ESCRT pathway. Extending from the older onset-age identified from this family, we found that comparing with the European and other populations, Asian patients displayed less proportion of severe patients and an older average age at onset. The origins of SPG80 patients associated with both their onset age and their disease severity, while the age at onset was not correlated with the disease severity.