Reabsorption of intervertebral disc prolapse after conservative treatment with traditional Chinese medicine: A case report.

BACKGROUND: Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation (LIDH) within a few weeks. CASE SUMMARY: Computed tomography and magnetic resonance imaging (MRI) of the lumbar region of a 25-year-old male diagnosed with LIDH showed prolapse of the L5/S2 disc. The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge. The patient elected a conservative treatment regimen that included traditional Chinese medicine (TCM), acupuncture, and massage. During a follow-up period of more than 12 mo, good improvement in pain was reported without complications. MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation. CONCLUSION: A conservative treatment regimen of TCM, acupuncture, and massage promoted reabsorption of a prolapsed disc.

Accurate dynamic 3D deformation measurement based on the synchronous multiplexing of polarization and speckle metrology.

An accurate dynamic 3D deformation measurement method realized by the combination of phase-shifting speckle interferometry and speckle correlation is proposed. By converting the speckle field and the reference field into a circular polarized and linear polarized state, the three-step phase-shifting speckle interferograms and one specklegram were recorded directly and simultaneously within a single image by using a polarization camera. Then, the out-of-plane deformation was demodulated from the synchronous phase-shifting fringe patterns, and the in-plane deformation was measured by performing correlation calculations by using specklegrams with the effect of the reference field ignored. Thus, the full-field 3D deformation was obtained precisely. Experimental results demonstrated the accuracy and dynamic measurement ability of the proposed method, which is compact and feasible for actual dynamic scenes.

Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas.

Diffuse large B-cell lymphoma (DLBCL) can be subdivided into activated B-cell like (ABC) and germinal center B-cell-like (GCB) DLCBL. Self-antigen engagement of B-cell receptors (BCRs) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-kB and PI3 kinase. Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase. We devised genome-wide CRISPR-Cas9 screens to identify regulators of IRF4, a direct transcriptional target of NF-kB and an indicator of proximal BCR signaling in ABC DLBCL. Unexpectedly, inactivation of N-linked protein glycosylation by the oligosaccharyltransferase-B (OST-B) complex reduced IRF4 expression. OST-B inhibition of BCR glycosylation reduced BCR clustering and internalization while promoting its association with CD22, which attenuated PI3 kinase and NF-kB activation. By directly interfering with proximal BCR signaling, OST-B inactivation killed models of ABC and GCB DLBCL, supporting the development of selective OST-B inhibitors for the treatment of these aggressive cancers.

Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway.

OBJECTIVE: Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. METHOD: ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. RESULT: The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. CONCLUSION: Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.

Morphology and deformity of the shoulder and pelvis in the entire spine radiographs of adolescent idiopathic scoliosis.

Background: To investigate the deformity and asymmetry of the shoulder and pelvis in adolescent idiopathic scoliosis (AIS) patients. Methods: This retrospective cross-sectional study enrolled 223 AIS patients with a right thoracic curve or left thoracolumbar/lumbar curve who underwent spine radiographs at the Third Hospital of Hebei Medical University between November 2020 and December 2021. The following parameters were measured: Cobb angle, clavicular angle, glenoid obliquity angle, acromioclavicular joint deviation, femoral neck-shaft projection angle, iliac obliquity angle, acetabular obliquity angle, coronal trunk deviation distance, and spinal deformity deviation distance. The Mann-Whitney U test, Kruskal-Wallis H test were used for inter-group comparisons, and Wilcoxon signed-rank test were used for intra-group left and right sides comparisons. Results: Shoulder and pelvic imbalances were found in 134 and 120 patients, respectively, and there were 87, 109, and 27 cases of mild, moderate, and severe scoliosis, respectively. Compared with mild scoliosis patients, the difference in the acromioclavicular joint offset on bilateral sides was significantly increased in moderate and severe scoliosis [11.04, 95% confidence interval (CI): 0.09-0.14 for mild, 0.13-0.17 for moderate, and 0.15-0.27 for severe scoliosis, P=0.004], and the difference in the femoral neck-shaft projection angle on bilateral sides was significantly enhanced with scoliosis aggravation (14.14, 95% CI: 2.34-3.41 for mild, 3.00-3.94 for moderate, and 3.57-6.43 for severe scoliosis, P=0.001). The acromioclavicular joint offset was significantly larger on the left than that on the right in patients with a thoracic curve or double curves (thoracic curve -2.75, 95% CI: 0.57-0.69 for the left and 0.50-0.63 for the right, P=0.006; double curve -3.27, 95% CI: 0.60-0.77 for the left and 0.48-0.65 for the right, P=0.001). The femoral neck-shaft projection angle was significantly larger on the left than right in patients with a thoracic curve (-4.46, 95% CI: 133.78-136.20 for the left and 131.62-134.01 for the right, P<0.001), but larger on the right than left in patients with thoracolumbar/lumbar curve (thoracolumbar -2.98, 95% CI: 133.75-136.70 for the left and 135.13-137.82 for the right, P=0.003; lumbar -3.24, 131.97-134.56 for the left and 133.76-136.26 for the right, P=0.001). Conclusions: In AIS patients, shoulder imbalance has a greater impact on coronal balance and spinal scoliosis above the lumbar segment, whereas pelvic imbalance has a greater impact on sagittal balance and spinal scoliosis below the thoracic segment.

Androgen Receptor Activation Induces Senescence in Thyroid Cancer Cells.

Thyroid cancer (TC) is the most common endocrine malignancy, with an approximately three-fold higher incidence in women. TCGA data indicate that androgen receptor (AR) RNA is significantly downregulated in PTC. In this study, AR-expressing 8505C (anaplastic TC) (84E7) and K1 (papillary TC) cells experienced an 80% decrease in proliferation over 6 days of exposure to physiological levels of 5α-dihydrotestosterone (DHT). In 84E7, continuous AR activation resulted in G1 growth arrest, accompanied by a flattened, vacuolized cell morphology, with enlargement of the cell and the nuclear area, which is indicative of senescence; this was substantiated by an increase in senescence-associated ß-galactosidase activity, total RNA and protein content, and reactive oxygen species. Additionally, the expression of tumor suppressor proteins p16, p21, and p27 was significantly increased. A non-inflammatory senescence-associated secretory profile was induced, significantly decreasing inflammatory cytokines and chemokines such as IL-6, IL-8, TNF, RANTES, and MCP-1; this is consistent with the lower incidence of thyroid inflammation and cancer in men. Migration increased six-fold, which is consistent with the clinical observation of increased lymph node metastasis in men. Proteolytic invasion potential was not significantly altered, which is consistent with unchanged MMP/TIMP expression. Our studies provide evidence that the induction of senescence is a novel function of AR activation in thyroid cancer cells, and may underlie the protective role of AR activation in the decreased incidence of TC in men.

An elevated preoperative cholesterol-to-lymphocyte ratio predicts unfavourable outcomes in colorectal cancer liver metastasis patients receiving simultaneous resections: a retrospective study.

BACKGROUND: To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases. METHODS: A total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden's index. Patients were divided into the CLR < 3.06 group and the CLR≥3.06 group. Propensity score matching analysis (PSM) and the inverse probability of treatment weighting (IPTW) method were conducted to eliminate bias between the two groups. The outcomes included short-term outcomes and long-term outcomes. Kaplan-Meier curves and log-rank tests were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS: In the short-term outcome analysis, after 1:1 PSM, 137 patients were distributed to the CLR < 3.06 group and CLR≥3.06 group. No significant difference was noted between the two groups (P > 0.1). Compared with patients with CLR < 3.06, patients with CLR≥3.06 had comparable operation times (320.0 [272.5-421.0] vs. 360.0 [292.5-434.5], P = 0.088), blood loss (200.0 [100.0-400.0] vs. 200.0 [150.0-450.0], P = 0.831), postoperative complication rates (50.4% vs. 46.7%, P = 0.546) and postoperative ICU rates (5.8% vs. 11.7%, P = 0.087). In the long-term outcome analysis, Kaplan-Meier analysis showed that compared with patients with CLR < 3.06, patients with CLR≥3.06 had worse PFS (P = 0.005, median: 10.2 months vs. 13.0 months) and OS (P = 0.002, median: 41.0 months vs. 70.9 months). IPTW-adjusted Kaplan-Meier analysis showed that the CLR≥3.06 group had worse PFS (P = 0.027) and OS (P = 0.010) than the CLR < 3.06 group. In the IPTW-adjusted Cox proportional hazards regression analysis, CLR≥3.06 was an independent factor for PFS (HR = 1.376, 95% CI 1.097-1.726, P = 0.006) and OS (HR = 1.723, 95% CI 1.218-2.439, P = 0.002). IPTW-adjusted Cox proportional hazards regression analysis including postoperative complications, operation time, intraoperative blood loss, intraoperative blood transfusion and postoperative chemotherapy revealed that CLR≥3.06 was an independent factor for PFS (HR = 1.617, 95% CI 1.252-2.090, P < 0.001) and OS (HR = 1.823, 95% CI 1.258-2.643, P = 0.002). CONCLUSIONS: The preoperative CLR level predicts unfavourable outcomes in CRLM patients receiving simultaneous resection of the primary lesion and liver metastases and should be taken into consideration when developing treatment and monitoring strategies.

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy.

Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF-α, IL-1ß, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1ß, IL-6, and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

Imbalance of Microbacterial Diversity Is Associated with Functional Prognosis of Stroke.

Objectives: There is mounting evidence to suggest that the pathophysiology of stroke is greatly influenced by the microbiota of the gut and its metabolites, in particular short-chain fatty acids (SCFAs). The primary purpose of the study was to evaluate whether the levels of SCFAs and the gut microbiota are altered in poststroke patients and to examine the relationship between these alterations and the physical condition, intestinal health, pain, or nutritional status of patients. Methods: Twenty stroke patients and twenty healthy controls were enrolled in the current study, and their demographics were matched. Gas chromatography was used to determine the fecal SCFAs, and 16S rRNA gene sequencing was used to evaluate their fecal microbiota. Microbial diversity and richness were examined using the diversity indices alpha and beta, and taxonomic analysis was utilized to determine group differences. The relationships between the gut microbiome and fecal SCFAs, discriminant bacteria, and poststroke clinical outcomes were analyzed. Results: Less community richness (ACE and Chao) was observed in the poststroke patients (P < 0.05), but the differences between the poststroke group and the healthy control group in terms of species diversity (Shannon and Simpson) were not statistically significant. The makeup of the poststroke gut microbiota was distinct from that of the control group, as evidenced by beta diversity. Then, the relative abundances of the taxa in the poststroke and control groups were compared in order to identify the specific microbiota changes. At the level of phylum, the poststroke subjects showed a significant increase in the relative abundances of Akkermansiaceae, Fusobacteriota, Desulfobacterota, Ruminococcaceae, and Oscillospirales and a particularly noticeable decrease in the relative abundance of Acidobacteriota compared to the control subjects (P < 0.05). In regard to SCFA concentrations, lower levels of fecal acetic acid (P = 0.001) and propionic acid (P = 0.049) were found in poststroke subjects. Agathobacter was highly correlated with acetic acid level (r = 0.473, P = 0.002), whereas Fusobacteria (r = -0.371, P = 0.018), Flavonifractor (r = -0.334, P = 0.034), Desulfovibrio (r = -0.362, P = 0.018), and Akkermansia (r = -0.321, P = 0.043) were negatively related to acetic acid levels. Additionally, the findings of the correlation analysis revealed that Akkermansia (r = -0.356, P = 0.024), Desulfovibrio (r = -0.316, P = 0.047), and Alloprevotella (r = -0.366, P = 0.020) were significantly negatively correlated with high-density lipoprotein cholesterol. In addition, the Neurogenic Bowel Dysfunction score (r = 0.495, P = 0.026), Barthel index (r = -0.531, P = 0.015), Fugl-Meyer Assessment score (r = -0.565, P = 0.009), Visual Analogue Scale score (r = 0.605, P = 0.005), and Brief Pain Inventory score (r = 0.507, P = 0.023) were significantly associated with alterations of distinctive gut microbiota. Conclusions: Stroke generates extensive and substantial alterations in the gut microbiota and SCFAs, according to our findings. The differences of intestinal flora and lower fecal SCFA levels are closely related to the physical function, intestinal function, pain, or nutritional status of poststroke patients. Treatment strategies aimed at modulating the gut microbiota and SCFAs may have the potential to enhance the clinical results of patients.

Polysaccharides from sea buckthorn (Hippophae rhamnoides L.) berries ameliorate cognitive dysfunction in AD mice induced by a combination of d-gal and AlCl3 by suppressing oxidative stress and inflammation reaction.

BACKGROUND: The therapeutic properties of Hippophae rhamnoides L. were known in Ancient Greece and in Tibetan and Mongolian medicine, which commonly used it for the treatment of heart ailments, rheumatism, and brain disorders. Modern studies have indicated that Hippophae rhamnoides L. polysaccharide (HRP) can improve cognitive impairment in mice with Alzheimer's disease (AD) but the specific mechanisms of the protective effect of HRP have not been elucidated fully. RESULTS: Our results showed that Hippophae rhamnoides L. polysaccharide I (HRPI) improved pathological behaviors related to memory and cognition, and reduced 1 Beta-amyloid (Aß) peptide deposition and neuronal cell necrosis. Pretreatment with Hippophae rhamnoides L. polysaccharide I (HRPI) also decreased the level of Toll-like receptor 4 (TLR4) and Myeloid differentiation factor 88 (MyD88), and reduced the release of inflammatory factors Tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in the brains of mice with AD. Treatment with HRPI also suppressed the expression level of Recombinant Kelch Like ECH Associated Protein 1 (KEAP1), and increased the levels of Nuclear factor erythroid 2-Related Factor 2 (Nrf2), antioxidant enzymes Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in the brains of AD mice. CONCLUSIONS: On the whole, these findings revealed that HRPI could improve the learning and memory ability and attenuate pathologic impairment in AD mice, and the underlying mechanisms may involve mediating oxidative stress and inflammation, possibly through the regulation of the Keap1/Nrf2 and TLR4/MyD88 signaling pathways. © 2023 Society of Chemical Industry.

Consistent functional abnormalities in patients with postpartum depression.

Postpartum depression (PPD) is a common public health concern. A wide range of functional abnormalities in various brain regions have been reported in fMRI studies on PPD, however, a consistent functional changing pattern is still lacking. Herein, we obtained functional Magnetic Resonance Imaging (fMRI) data from 52 patients with PPD and 24 healthy postpartum women (HPW). Functional indexes (low-frequency fluctuation, degree centrality, and regional homogeneity) were calculated and compared among these groups to explore the functional changing patterns of PPD. Then, correlation analyses were performed to investigate the relationship between changed functional indexes and clinical measurements in the PPD. Finally, support vector machine (SVM) was performed to test whether these abnormal features can be used to distinguish PPD from HPW. As a result, we identified significantly and consistently functional changing pattern characterizing by increased functional activity in the left inferior occipital gyrus and decreased functional activity right anterior cingulate cortex in the PPD as compared to HPW. These functional values in the right anterior cingulate cortex were significantly correlated with depression symptoms in the PPD, and can be used as features to distinguish PPD from HPW. In conclusion, our results suggested that the right anterior cingulate cortex could be served as a functional neuro-imaging biomarker for PPD, which might be used as a potential target for neuro-modulation.

Misdiagnosis of scalp angiosarcoma: A case report.

BACKGROUND: Angiosarcoma is a rare malignant tumor. Owing to the lack of specific clinical manifestations of this disease, it is difficult to achieve early diagnosis and start early treatment. CASE SUMMARY: A 78-year-old male patient was admitted to the hospital because of a bump on his head that did not heal for 4 mo. The patient was diagnosed with a refractory head wound. The patient underwent neoplasm resection and skin grafting surgery in the Plastic Surgery. The neoplasm was sent for pathological examination during the operation. The final pathological results were confirmed scalp angiosarcoma. CONCLUSION: Our research suggests that pathological examination should be performed for refractory ulcers of the scalp, and physical factor therapy should be used with caution before the diagnosis is clear.

A Stretchable Solid Ionic Electrode-Based Triboelectric Nanogenerator for Biomechanical Energy Harvesting and Self-Powered Sensors.

Stretchable power devices and self-powered sensors have become increasingly desired for wearable electronics and artificial intelligence. In this study, an all-solid-state triboelectric nanogenerator (TENG) is reported, whose one solid-state structure prevents delamination during stretch and release cycles and increasing the patch adhesive force (3.5 N) and strain (586% elongation at break). Through the synergetic virtues of stretchability, ionic conductivity, and excellent adhesion to the tribo-layer, reproducible open-circuit voltage (VOC ) of 84 V, charge (QSC ) of 27.5 nC, and short-circuit current (ISC ) of 3.1 µA after drying at 60°C or 20,000 contact-separation cycles are obtained. Apart from contact-separation, this device shows unprecedented electricity generation through stretch-release of solid materials leading to a linear relationship between VOC and strain. For the first time, this work provides a clear explanation of the working mechanism of contact-free stretching-releasing and investigates the relationships of exerted force, strain, thickness of the device, and electric output. Benefitting from the one solid-state structure, this contact-free device remains stable even after repeated stretch-release cycling, maintaining 100% of its VOC after 2500 stretch-release cycles. These findings provide a strategy toward highly conductive and stretchable electrodes for harvesting mechanical energy and health monitoring.

Global research trends in prediction of difficult airways: A bibliometric and visualization study.

Many tools are used to predict difficult airway, including bedside screening tests, radiological variables, and ultrasonography. However, the "gold standard" to identify difficult airway before intubation has not been established. The assessment and prediction of difficult airway is receiving increasing attention in clinical practice due to the devastating results of failed oxygenation or intubation. A literature visualization study is necessary to understand the research trend and help tailor future research directions. Science citation index-expanded web of Science database were used to search for literature related to assessment and prediction of difficult airways published before May 9th, 2022. VOS viewer software was used for visual analysis, including literature statistics, and co-occurrence analysis. A total of 2609 articles were included. The amount of relevant research interest and literature is increasing every year. According to co-occurrence network analysis, the research results can be grouped into the following 5 clusters, intubation approaches, intubation in special populations, difficult airway assessment tests, intubation in critical care/emergency settings and education, and laryngoscopes. Co-occurrence overlay analysis showed that video laryngoscopes and index prediction (including computed tomography and ultrasonography), emerged recently and comprised an important percentage of current studies. It can be predicted that future studies should focus on understanding the upper airway anatomy and constructing risk index predictions. Based on current global research trends, risk index predictions are the next hot topics in the evaluation and prediction of difficult airways, and video laryngoscopes will continue to be a hot topic in this field.

Phylogeny-Related Variations in Venomics: A Test in a Subset of Habu Snakes (Protobothrops).

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.

Kupffer cell pyroptosis mediated by METTL3 contributes to the progression of alcoholic steatohepatitis.

Chronic alcohol consumption is a major risk factor for alcoholic steatohepatitis (ASH). Previous studies have shown that direct injury of hepatocytes is the key factor in its occurrence and development. However, our study shows that the role of Kupffer cells in ASH cannot be ignored. We isolated Kupffer cells from the livers of ASH mice and found that alcohol consumption induced Kupffer cell pyroptosis and increased the release of interleukin-1ß (IL-1ß). Furthermore, we screened the related m6A enzyme methyltransferase-like 3 (METTL3) from liver Kupffer cells, and found that silencing METTL3 alleviated inflammatory cytokine eruption by Kupffer cell pyroptosis in ASH mice. In vitro, we silenced METTL3 with lentivirus in BMDMs and RAW264.7 cells and confirmed that METTL3 could reduce pyroptosis by influencing the splicing of pri-miR-34A. Together, our results revealed a critical role of KC pyroptosis in ASH and highlighted the mechanism by which METLL3 relieves cell pyroptosis, which could be a promising therapeutic strategy for ASH.

Quantifying traffic-related carbon emissions on elevated roads through on-road measurements.

Vehicles generally move smoothly and with high speeds on elevated roads, thereby producing specific traffic-related carbon emissions in contrast to ground roads. Hence, a portable emission measurement system was adopted to determine traffic-related carbon emissions. The on-road measurement results revealed that the instantaneous emissions of CO2 and CO from elevated vehicles were 17.8% and 21.9% higher than those from ground vehicles, respectively. Based on it, the vehicle specific power was confirmed to exhibit a positive exponential relationship with instantaneous CO2 and CO emissions. In addition to carbon emissions, carbon concentrations on roads were simultaneously measured. The average CO2 and CO emissions on elevated roads in urban areas were 1.2% and 6.9% higher than those on ground roads, individually. Finally, a numerical simulation was performed, and the results verified that elevated roads could deteriorate the air quality on ground roads but improve the air quality above them. What ought to be paid attention to is that the elevated roads present varied traffic behaviour and cause particular carbon emissions, indicating that comprehensive consideration and further balance among the traffic-related carbon emissions are necessary when building elevated roads to alleviate the traffic congestion in urban areas.

Immunobiology and Host Response to HEV.

Hepatitis E virus (HEV) usually causes acute self-limiting hepatitis but sometimes leads to chronic infection in immunocompromised persons. HEV is not directly cytopathic. Immunologically mediated events after HEV infection are believed to play important roles in the pathogenesis and clearance of infection. The anti-HEV antibody responses have been largely clarified since the determination of major antigenic determinant of HEV, which is located in the C-terminal portion of ORF2. This major antigenic determinant also forms the conformational neutralization epitopes. Robust anti-HEV immunoglobulin M (IgM) and IgG responses usually develop 3-4 weeks after infection in experimentally infected nonhuman primates. In humans, potent specific IgM and IgG responses occur in the very early phase of the disease and are critical in eliminating the virus, in concert with the innate and adaptive T-cell immune responses. Testing anti-HEV IgM is valuable in the diagnosis of acute hepatitis E. The long-term persistence and protection of anti-HEV IgG provide the basis for estimating the prevalence of HEV infection and for the development of a hepatitis E vaccine. Although human HEV has four genotypes, all the viral strains are considered to belong to a single serotype. It is becoming increasingly clear that the innate and adaptive T-cell immune responses play critical roles in the clearance of the virus. Potent and multispecific CD4+ and CD8+ T cell responses to the ORF2 protein occur in patients with acute hepatitis E, and weaker HEV-specific CD4+ and CD8+ T cell responses appear to be associated with chronic hepatitis E in immunocompromised individuals.

Cerium-modified amorphous manganese oxides for efficient catalytic removal of ozone.

Manganese-based catalysts were widely developed for catalytic removal of ozone, and the low stability and water inactivation are major challenges. To improve removal performance of ozone, three methods were applied to modify amorphous manganese oxides, including acidification, calcination and Ce modification. The physiochemical properties of prepared samples were characterized, and the catalytic activity for ozone removal was evaluated. All modification methods can promote the removal of ozone by amorphous manganese oxides, and Ce modification showed the most significant enhancement. It was confirmed that the introduction of Ce markedly changed the amount and property of oxygen vacancies in amorphous manganese oxides. Superior catalytic activity of Ce-MnOx can be ascribed to its more content and enhanced formation ability of oxygen vacancies, larger specific surface area and higher oxygen mobility. Furthermore, the durability tests under high relative humidity (80%) determined that Ce-MnOx showed excellent stability and water resistance. These demonstrate the promising potential of amorphously Ce-modified manganese oxides for catalytic removal of ozone.

Comparability of Osteoporosis Treatment Groups Among Female Medicare Beneficiaries in the United States.

It is often difficult to obtain valid estimates of comparative treatment effectiveness and safety owing to differences across patient populations taking different medications in the real world. One approach for assessing comparability between treatment groups in effectiveness studies is to use negative control outcomes (NCOs). NCOs share similar sources of bias with the primary outcomes but have no plausible causal relationship to the treatment of interest. Observing differences in the risk of NCOs thus provides evidence for residual confounding between groups. This retrospective study assessed the comparability of postmenopausal women, treated with osteoporosis medications with various mechanisms of action such as denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor), zoledronic acid (bisphosphonate derivative), or oral bisphosphonates including alendronate. Administrative claims data were extracted from the US Centers for Medicare and Medicaid Services' Chronic Condition Warehouse database (May 2010-December 2016). Propensity scores were used to match denosumab patients 1:1 to comparators. Four nonfracture NCOs and three early fracture NCOs (before substantial biologic effects of treatment would be expected) were assessed over 1-year and 3-month follow-up periods, respectively. According to comparability decision rules established a priori, patients initiating denosumab were comparable to those initiating zoledronic acid or alendronate, irrespective of prior osteoporosis treatment experience. Among new users, new switchers, and in the historical fracture subgroup, no meaningful differences were observed in the cumulative incidence of the seven NCOs comparing denosumab to zoledronic acid. This empirical examination can assist in the selection of appropriate comparator groups for future comparability research using real-world data. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).