Biyang floral mushroom-derived exosome-like nanovesicles: characterization, absorption stability and ionizing radiation protection.

Diet-derived exosome-like nanovesicles are a class of natural active substances that have similar structures and functions to mammalian exosomes. Biyang floral mushrooms and their active extracts have been found to possess radioprotective effects and to deeply explore their novel active substances, the radioprotective effects of Biyang floral mushroom-derived exosome-like nanovesicles (BFMELNs) were investigated in this study. Results showed that these surface-negatively charged vesicles possessed an ideal size and good stability against environmental changes such as temperature and gastrointestinal digestion. Furthermore, BFMELNs could effectively be taken up by HL-7702 cells and Caco-2 cells through cellular phagocytosis mediated by clathrin and dynein. Emphatically, BFMELNs with an exosome-like morphology contained RNA, proteins, lipids, polyphenols and flavonoids to exert good antioxidant and radioprotective effects in vitro. Meanwhile, BFMELNs also exhibited good radioprotective effects by restoring peripheral blood indexes, mitigating damage to organs, and regulating the redox state in mice. Collectively, BFMELNs showed promise as novel and natural radioprotective nano-agents for preventing IR-induced oxidative stress damage.

A two-center randomized controlled trial of a repairing mask as an adjunctive treatment for mild to moderate rosacea.

OBJECTIVE: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. METHODS: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. RESULTS: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. CONCLUSION: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use.

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway.

BACKGROUND: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances. METHODS: An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH. RESULTS: SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples. CONCLUSION: In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.

Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk.

Insight into associations between the gut microbiome with metabolism and aging is crucial for tailoring interventions to promote healthy longevity. In a discovery cohort of 10,207 individuals aged 40-93 years, we used 21 metabolic parameters to classify individuals into five clusters, termed metabolic multimorbidity clusters (MCs), that represent different metabolic subphenotypes. Compared to the cluster classified as metabolically healthy (MC1), clusters classified as 'obesity-related mixed' (MC4) and 'hyperglycemia' (MC5) exhibited an increased 11.1-year cardiovascular disease (CVD) risk by 75% (multivariable-adjusted hazard ratio (HR): 1.75, 95% confidence interval (CI): 1.43-2.14) and by 117% (2.17, 1.72-2.74), respectively. These associations were replicated in a second cohort of 9,061 individuals with a 10.0-year follow-up. Based on analysis of 4,491 shotgun fecal metagenomes from the discovery cohort, we found that gut microbial composition was associated with both MCs and age. Next, using 55 age-specific microbial species to capture biological age, we developed a gut microbial age (MA) metric, which was validated in four external cohorts comprising 4,425 metagenomic samples. Among individuals aged 60 years or older, the increased CVD risk associated with MC4 or MC5, as compared to MC1, MC2 or MC3, was exacerbated in individuals with high MA but diminished in individuals with low MA, independent of age, sex and other lifestyle and dietary factors. This pattern, in which younger MA appears to counteract the CVD risk attributable to metabolic dysfunction, implies a modulating role of MA in cardiovascular health for metabolically unhealthy older people.

Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein.

Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.

Gas6-Axl signal promotes indoor VOCs exposure-induced pulmonary fibrosis via pulmonary microvascular endothelial cells-fibroblasts cross-talk.

Volatile organic compounds (VOCs) as environmental pollutants were associated with respiratory diseases. Pulmonary fibrosis (PF) was characterized by an increase of extracellular matrix, leading to deterioration of lung function. The adverse effects on lung and the potential mechanism underlying VOCs induced PF had not been elucidated clearly. In this study, the indoor VOCs exposure mouse model along with an ex vivo biosensor assay was established. Based on scRNA-seq analysis, the adverse effects on lung and potential molecular mechanism were studied. Herein, the results showed that VOCs exposure from indoor decoration contributed to decreased lung function and facilitated pulmonary fibrosis in mice. Then, the whole lung cell atlas after VOCs exposure and the heterogeneity of fibroblasts were revealed. We explored the molecular interactions among various pulmonary cells, suggesting that endothelial cells contributed to fibroblasts activation in response to VOCs exposure. Mechanistically, pulmonary microvascular endothelial cells (MPVECs) secreted Gas6 after VOCs-induced PANoptosis phenotype, bound to the Axl in fibroblasts, and then activated fibroblasts. Moreover, Atf3 as the key gene negatively regulated PANoptosis phenotype to ameliorate fibrosis induced by VOCs exposure. These novel findings provided a new perspective about MPVECs could serve as the initiating factor of PF induced by VOCs exposure.

Pathology of pain and its implications for therapeutic interventions.

Pain is estimated to affect more than 20% of the global population, imposing incalculable health and economic burdens. Effective pain management is crucial for individuals suffering from pain. However, the current methods for pain assessment and treatment fall short of clinical needs. Benefiting from advances in neuroscience and biotechnology, the neuronal circuits and molecular mechanisms critically involved in pain modulation have been elucidated. These research achievements have incited progress in identifying new diagnostic and therapeutic targets. In this review, we first introduce fundamental knowledge about pain, setting the stage for the subsequent contents. The review next delves into the molecular mechanisms underlying pain disorders, including gene mutation, epigenetic modification, posttranslational modification, inflammasome, signaling pathways and microbiota. To better present a comprehensive view of pain research, two prominent issues, sexual dimorphism and pain comorbidities, are discussed in detail based on current findings. The status quo of pain evaluation and manipulation is summarized. A series of improved and innovative pain management strategies, such as gene therapy, monoclonal antibody, brain-computer interface and microbial intervention, are making strides towards clinical application. We highlight existing limitations and future directions for enhancing the quality of preclinical and clinical research. Efforts to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice, thereby improving pain management from bench to bedside.

Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

Comparison of craniomaxillofacial morphology in children with unilateral cleft lip and palate treated with/without presurgical nasoalveolar molding - a retrospective study with a mean age of 5 years.

OBJECTIVES: To three-dimensionally assess differences in craniomaxillofacial skeletal development in patients with operated unilateral cleft lip and palate (UCLP) treated with/without presurgical nasoalveolar molding (PNAM) with a mean age of 5 years. MATERIALS AND METHODS: Cone-beam CT radiographs of 30 patients with UCLP who had undergone PNAM and 34 patients with UCLP who did not receive PNAM were analyzed. The data were stored in DICOM file format and were imported into the Dolphin Imaging program for 3D image reconstruction and landmark identification. 33 landmarks, 17 linear and three angular variables representing craniofacial morphology were analyzed and compared by using the Mann-Whitney U tests. RESULTS: The vast majority of linear variables and 3D coordinates of landmark points reflecting craniofacial skeletal symmetry were not significantly different between the two groups. In terms of craniofacial skeletal development, the PNAM group had a significantly smaller anterior nasal spine offset in the midsagittal plane and a greater maxillary length compared to the non-PNAM group. CONCLUSIONS: Evaluations performed in early childhood showed that treatment with/without PNAM in the neonatal period was not a major factor influencing craniomaxillofacial hard tissue development in patients with UCLP; moreover, PNAM treatment showed significant correction of skeletal deviation at the base of the nose. CLINICAL RELEVANCE: Follow-up in early childhood has shown that PNAM treatment administered during the neonatal stage does not impede maxillary development and has benefits in correcting nasal floor deviation. It is a viable option for improving nasal deformity in children with unilateral cleft lip and palate.

Experimental Study on the Response of Cracked Sandstone to the Intermediate Principal Stress Coupled with Pore Pressure.

Underground fractured rock masses are susceptible to failure under the combined influence of true triaxial stresses and pore pressure, posing severe threats to personnel and production safety of underground engineering. To investigate the influence of intermediate principal stress (σ2) on the mechanical and water diffusion volume change (ΔV) characteristics during the failure process of cracked rocks under stable pore pressure, this study conducted true triaxial strength experiments on cracked sandstone with stable pore pressure. The results demonstrated that with the increase of σ2, crack initiation stress (σci), crack damage stress (σcd) and the peak stress (σ1,peak) of cracked sandstone initially increase and then decrease. Conversely, ΔV tends to decrease first and then increase with the increase of σ2. This inverse relationship indicates that under elevated σ2, the decreased strength of cracked rock could lead to an increase in ΔV, which may increase the probability of water inrush disasters. The findings of this study provide a theoretical reference for the stability of rock mass engineering and the prevention of water inrush disasters.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Triply Interlocked [2]catenanes: Rational Synthesis, Reversible Conversion Studies and Unprecedented Application in Photothermal Responsive Elastomer.

Triply interlocked [2]catenane complexes featuring two identical, mechanically interlocked units are extraordinarily rare chemical compounds, whose properties and applications remain open to detailed studies. Herein, we introduce the rational design of a new ligand precursor, L1, suitable for the synthesis of six triply interlocked [2]catenanes by coordination-driven self-assembly. The interlocked compounds can be reversibly converted into the corresponding simple triangular prism metallacage by addition of H2O or DMF solvents to their CH3OH solutions, thereby demonstrating the importance of π···π stacking and hydrogen bonding interactions in the formation of triply interlocked [2]catenanes. Moreover, extensive studies have been conducted to assess the remarkable photothermal conversion performance. Complex 6a, exhibiting outstanding photothermal conversion performance (conversion efficiency in solution : 31.82%), is used to prepare novel photoresponsive elastomer in combination with thermally activated liquid crystal elastomer. The resultant material displays robust response to near-infrared (NIR) laser and the capability of completely reforming the shape and reversible actuation, paving the way for the application of half-sandwich organometallic units in photo-responsive smart materials.

Dendritic boron and nitrogen doped high-entropy alloy porous carbon fibers for high-efficiency hydrogen evolution reaction.

Among various electrocatalysts, high-entropy alloys (HEAs) have gained significant attention for their unique properties and excellent catalytic activity in the hydrogen evolution reaction (HER). However, the precise synthesis of HEA catalysts in small sizes remains challenging, which limits further improvement in their catalytic performance. In this study, boron- and nitrogen-doped HEA porous carbon nanofibers (HE-BN/PCNF) with an in situ-grown dendritic structure were successfully prepared, inspired by the germination and growth of tree branches. Furthermore, the dendritic fibers constrained the growth of HEA particles, leading to the synthesis of quantum dot-sized (1.67 nm) HEA particles, which also provide a pathway for designing HEA quantum dots in the future. This work provides design ideas and guiding suggestions for the preparation of borated HEA fibers with different elemental combinations and for the application of dendritic nanofibers in various fields.

ROF-2 as an Aggregation-Induced Emission (AIE) Probe for Multi-Target Amyloid Detection and Screening of Amyloid Inhibitors.

Misfolding and aggregation of amyloid peptides into ß-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation-induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported. As an amyloid probe, ROF2 outperformed ThT, demonstrating its superior sensing capability in monitoring, detecting, and distinguishing amyloid aggregates of different sequences (Amyloid-ß, human islet amyloid polypeptide, or human calcitonin) and sizes (monomers, oligomers, or fibrils). More importantly, the utilization of ROF2 as a screening molecule to identify and repurpose cardiovascular drugs as amyloid inhibitors is introduced. These drugs exhibit potent amyloid inhibition properties, effectively preventing amyloid aggregation and reducing amyloid-induced cytotoxicity both in cells and nematode. The findings present a novel strategy to discovery AIE-based amyloid probes and to be used to repurpose amyloid inhibitors, expanding diagnostic and therapeutic options for neurodegenerative diseases while addressing vascular congestion and amyloid aggregation risks.

Auditory Effects of Acoustic Noise From 3-T Brain MRI in Neonates With Hearing Protection.

BACKGROUND: Neonates with immature auditory function (eg, weak/absent middle ear muscle reflex) could conceivably be vulnerable to noise-induced hearing loss; however, it is unclear if neonates show evidence of hearing loss following MRI acoustic noise exposure. PURPOSE: To explore the auditory effects of MRI acoustic noise in neonates. STUDY TYPE: Prospective. SUBJECTS: Two independent cohorts of neonates (N = 19 and N = 18; mean gestational-age, 38.75 ± 2.18 and 39.01 ± 1.83 weeks). FIELD STRENGTH/SEQUENCE: T1-weighted three-dimensional gradient-echo sequence, T2-weighted fast spin-echo sequence, single-shot echo-planar imaging-based diffusion-tensor imaging, single-shot echo-planar imaging-based diffusion-kurtosis imaging and T2-weighted fluid-attenuated inversion recovery sequence at 3.0 T. ASSESSMENT: All neonates wore ear protection during scan protocols lasted ~40 minutes. Equivalent sound pressure levels (SPLs) were measured for both cohorts. In cohort1, left- and right-ear auditory brainstem response (ABR) was measured before (baseline) and after (follow-up) MRI, included assessment of ABR threshold, wave I, III and V latencies and interpeak interval to determine the functional status of auditory nerve and brainstem. In cohort2, baseline and follow-up left- and right-ear distortion product otoacoustic emission (DPOAE) amplitudes were assessed at 1.2 to 7.0 kHz to determine cochlear function. STATISTICAL TEST: Wilcoxon signed-rank or paired t-tests with Bonferroni's correction were used to compare the differences between baseline and follow-up ABR and DPOAE measures. RESULTS: Equivalent SPLs ranged from 103.5 to 113.6 dBA. No significant differences between baseline and follow-up were detected in left- or right-ear ABR measures (P > 0.999, Bonferroni corrected) in cohort1, or in DPOAE levels at 1.2 to 7.0 kHz in cohort2 (all P > 0.999 Bonferroni corrected except for left-ear levels at 3.5 and 7.0 kHz with corrected P = 0.138 and P = 0.533). DATA CONCLUSION: A single 40-minute 3-T MRI with equivalent SPLs of 103.5-113.6 dBA did not result in significant transient disruption of auditory function, as measured by ABR and DPOAE, in neonates with adequate hearing protection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 5.

Prognostic value of pathological nodal burden after neoadjuvant chemotherapy in initially cN0-1 breast cancer patients: a dual-center, 10-year survival analysis.

Background: There is an interest in performing de-escalating axillary surgery after neoadjuvant chemotherapy (NAC). However, the significance of residual axillary node disease after NAC has not been well studied. Objectives: To investigate the pathological residual axillary lymph node tumor burden (ypN) of patients with initial clinical nodal stage cN0-1 breast cancer after NAC and determine its prognostic value. Design: Initial cN0-1 breast cancer patients who received NAC followed by axillary surgery at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University between January 2011 and December 2019 were included. Methods: Survival outcomes were compared according to different clinical and pathological stage and nodal response to NAC. The main outcomes were disease-free survival (DFS) and overall survival (OS). Factors associated with survival were defined by Cox regression analysis. Results: A total of 911 patients were included, among whom 260 had cN0 and 651 had cN1 tumors. After NAC, 410 patients were ypN0, and another 501 were ypN+. The median follow-up time was 63 months. There was no significant difference in DFS or OS between the cN0 and cN1 groups in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+) and HR-/HER2- subtypes; instead, ypN status was significantly related to DFS and OS. In HR+/HER2- subtype, both cN and ypN stages did not show significant survival differences, but the ypN number and the nodal response to NAC showed significant prognostic value (p < 0.05). Among HR-/HER2+ patients, all cN status, ypN status, ypN number, and nodal response were significantly associated with survival (p < 0.05). Furthermore, tumor biology, axillary surgery, ypN status, pathological tumor size, and radiotherapy were independent prognostic factors for DFS and OS. Conclusion: The ypN status after NAC provide more prognostic information than the initial cN stage in cN0-1 patients, and the surgical axillary staging after NAC may have high clinical value.

Allosteric Regulation and Inhibition of Coronavirus 3CLpro Revealed by HDX-MS.

Coronavirus (CoV) infections have caused contagious and fatal respiratory diseases in humans worldwide. CoV 3-chymotrypsin-like proteases (3CLpro or Mpro) play an important role in viral maturation, and maintenance of their dimeric conformation is crucial for viral activity. Therefore, allosterically regulated dimerization of 3CLpro can be employed as a drug development target. Here, we investigated the allosteric regulatory mechanism of 3CLpro dimerization by using hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) technology. We found that the FLAG tag directly coupled to the N-finger of 3CLpro significantly increased HDX kinetics at the dimer interface, and 3CLpro transformed from a dimer to a monomer. The 3CLpro mutants of SARS-CoV-2, which are monomeric, also exhibited increased deuterium exchange. Binding of the allosteric inhibitor Gastrodenol to most betacoronavirus 3CLpros led to increased allosteric deuterium exchange, resulting in the monomeric conformation of the CoV 3CLpro upon binding. Molecular dynamics (MD) simulation analysis further indicated the molecular mechanism of action of Gastrodenol on CoV 3CLpro: binding of Gastrodenol to SARS-CoV-2 3CLpro destroyed the hydrogen bond in the dimer interface. These results suggest that Gastrodenol may be a potential broad-spectrum anti-betacoronavirus drug.

Comparison of treatment effects between clear aligners and fixed appliances in patients treated with miniscrew-assisted molar distalization.

OBJECTIVES: The biomechanics in achieving molar distalization may differ between fixed appliances and clear aligners in the control of tooth movement. The objective of this study was to compare the treatment effects between clear aligners (CA) and fixed appliances (FA) in patients treated with miniscrew-assisted molar distalization. METHODS: The sample consisted of 46 subjects with mild-to-moderate crowding. A total of 22 patients treated with clear aligners (age, 25.66 ±â€…6.11 years old) and 24 patients treated with fixed appliances (age, 24.04 ±â€…4.95 years old) for miniscrew-assisted molar distalization were included in this study. The dental and skeletal changes were evaluated by the pre- and post-treatment lateral cephalograms. RESULTS: Significant changes were found with the vertical variables SN-OP angle (2.24 ±â€…3.22°, P < .05) and SN-MP angle (0.73 ±â€…1.15°, P < .05) for the FA group when compared with the CA group (SN-OP angle 0.41 ±â€…2.26° and SN-MP angle -0.21 ±â€…1.38°, P > .05). Both treatment groups achieved a 2-3 mm. molar distalization with significant intrusion of the upper molars. The CA group showed significantly less distal tipping of molars (U6^PP angle -2.29 ±â€…3.29° and L6^MP angle -2.92 ±â€…2.49°, P < .05) compared to the FA group (-5.24 ±â€…4.28° and -5.53 ±â€…5.03°, P < .05). In addition, significant retraction and lingual inclination of the upper and lower incisors were found in both groups. LIMITATIONS: The changes of tooth position were evaluated by 2D lateral cephalograms, not 3D measurements. CONCLUSIONS: Compared to fixed appliances, clear aligners seemed to have better control of vertical dimension and distal tipping of molars in patients treated with miniscrew-assisted molar distalization.

Research Progress of Natural Active Substances with Immunosuppressive Activity.

The increasing prevalence of autoimmune diseases globally has prompted extensive research and the development of immunosuppressants. Currently, immunosuppressive drugs such as cyclosporine, rapamycin, and tacrolimus have been utilized in clinical practice. However, long-term use of these drugs may lead to a series of adverse effects. Therefore, there is an urgent need to explore novel drug candidates for treating autoimmune diseases. This review aims to find potential candidate molecules for natural immunosuppressive compounds derived from plants, animals, and fungi over the past decade. These compounds include terpenoids, alkaloids, phenolic compounds, flavonoids, and others. Among them, compounds 49, 151, 173, 200, 204, and 247 have excellent activity; their IC50 were less than 1 µM. A total of 109 compounds have good immunosuppressive activity, with IC50 ranging from 1 to 10 µM. These active compounds have high medicinal potential. The names, sources, structures, immunosuppressive activity, and the structure-activity relationship were summarized and analyzed.