Uncovering the Intrinsic High Fracture Toughness of Titanium via Lowered Oxygen Impurity Content.

Titanium (Ti) and its alloys are known to exhibit room-temperature fracture toughness below 130 MPa m1/2, only about one half of the best austenitic stainless steels. It is purported that this is not the best possible fracture resistance of Ti, but a result of oxygen impurities that sensitively retard the activities of plasticity carriers in this hexagonal close-packed metal. By a reduction of oxygen content from the 0.14 wt% in commercial purity Ti to 0.02 wt%, the mode-Ι fracture toughness of the low-oxygen Ti is measured to be as high as KJ Ic ≈ 255 MPa m1/2, corresponding to J-integral-based crack-initiation toughness of up to JIc ≈ 537 kJ m-2. This extraordinary toughness, reported here for the first time for pure Ti, places Ti among the toughest known materials. The intrinsic high fracture resistance is attributed to the profuse plastic deformation in a significantly enlarged plastic zone, rendered by the pronounced deformation twinning ahead of the crack tip along with ample twin-stimulated 〈c+a〉 dislocation activities, in the absence of impeding oxygen. Controlling the content of a property-controlling impurity thus holds the promise to be a readily applicable strategy to reach for unprecedented damage tolerance in some other structural alloys.

Cadmium causes spleen toxicity in chickens by regulating mitochondrial unfolded protein response and nuclear receptors response.

Cadmium (Cd) is a heavy metal that pollutes the environment and threatens human and animal health via the food chain. The spleen is one of the target organs affected by Cd toxicity. However, the mechanism of Cd toxicity is not fully understood. In this study, 80 chicks were allocated into 4 groups (n = 20) and exposed to different doses of CdCl2 (0 mg/kg, 35 mg/kg, 70 mg/kg and 140 mg/kg) for 90 d. The pathological changes in the spleen, mitochondrial dynamics-related factors, cytochrome P450 (CYP450) enzyme system contents, activities, transcription levels, nuclear receptors (NRs) response molecule levels, and mitochondrial unfolded protein-related factors were detected. The findings indicate that exposure to Cd significantly leads to spleen injury. In Cd groups, the total contents of CYP450 and cytochrome b5 (Cyt b5) increased, and the activities of the CYP450 enzyme system (APND, ERND, AH, and NCR) changed. The NRs response was induced, and the gene levels of AHR/CAR and corresponding CYP450 isoforms (CYP1B1, CYP1A5, CYP1A1, CYP2C18, CYP2D6 and CYP3A4) were found altered. The study found that Cd exposure altered the mRNA expression levels of mitochondrial dynamics-related factors, such as OPA1, Fis1, MFF, Mfn1, and Mfn2, breaking mitochondrial fusion and cleavage and ultimately leading to mitochondrial dysfunction. Changes were detected in the gene levels of several mitochondrial unfolded protein response (mtUPR)-related factors, namely (SIRT1, PGC-1α, NRF1, TFAM, SOD2, and HtrA2). Cd also altered the gene levels of mitochondrial function-related factors (VDAC1, Cyt-C, COA6, PRDX3, RAF and SIRT3). It is showed that Cd can initiate the NRs response, influence the homeostasis of the CPY450 enzyme system, trigger the mtUPR, impair mitochondrial function, and ultimately lead to Cd toxicity in the spleen of chickens.

Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study.

BACKGROUND: Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM: To explore endoscopic detection and diagnostic strategies for MGCs. METHODS: This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS: All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION: WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.

An updated and comprehensive review of the morphology, ethnomedicinal uses, phytochemistry, and pharmacological activity of Aster tataricus L. f.

Ethnopharmacological relevance: Aster tataricus L.f., an extensively used herb in traditional Chinese medicine for more than 2000 years, is known as "Zi wan" or "Fan huncao". Its dried root and rhizome hold great promise in the treatment of cough, asthma, tumor, inflammation, etc.Aim of the study: This literature review summarizes the morphology characteristics, ethnopharmacological use, phytochemical properties, pharmacological effects, and potential applications of Aster tataricus. Furthermore, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Using "Aster tataricus L.f.", "Traditional medicinal usage", "Phytochemistry", "Pharmacological effects" as the keywords and gathered relevant data on Aster tataricus L.f. using electronic databases (Elsevier, PubMed, ACS, CNKI, Google Scholar, Baidu Scholar, Web of Science), relevant books, and classic literature about Chinese herb. Result: A total of 186 compounds have been isolated and identified from Aster tataricus, including terpenes, organic acids, peptides, and flavonoids. And Aster tataricus has been widely used as a natural cough suppressant and has anti-oxidative, anti-inflammatory, anti-depressive, and anti-tumor effects. In addition, Aster tataricus has also been reported to have damaging effects on the liver as well as other toxicities were discussed in this review. Conclusions: Aster tataricus is an ancient herbal medicine with a broad spectrum of pharmaco logical activities that has been used for thousands of years in China, and has shown remarkable effectiveness in the treatment of various diseases, especially cough, asthma, inflammation. Although its rich chemical constituents have various pharmacological activities, the underlying mechanisms, as well as its toxicity and safety, remains unclear and warrant further investigation.

Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.

The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast.

BACKGROUND: Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. AIM: To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. RESULTS: In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). CONCLUSION: While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.

In-situ Ti4+-doped modification of layer-structured Ni-rich LiNi0.83Co0.11Mn0.06O2 cathode materials for high-energy lithium-ion batteries.

The further commercialization of layer-structured Ni-rich LiNi0.83Co0.11Mn0.06O2 (NCM83) cathode for high-energy lithium-ion batteries (LIBs) has been challenged by severe capacity decay and thermal instability owing to the microcracks and harmful phase transitions. Herein, Ti4+-doped NCM83 cathode materials are rationally designed via a simple and low-cost in-situ modification method to improve the crystal structure and electrode-electrolyte interface stability by inhibiting irreversible polarizations and harmful phase transitions of the NCM83 cathode materials due to Ti4+-doped forms stronger metal-O bonds and a stable bulk structural. In addition, the optimal doping amount of the composite cathode material is also determined through the results of physical characterization and electrochemical performance testing. The optimized Ti4+-doped NCM83 cathode material presents wider Li+ ions diffusion channels (c = 14.1687 Å), lower Li+/Ni2+ mixing degree (2.68 %), and compact bulk structure. The cell assembled with the optimized Ti4+-doped NCM83 cathode material exhibits remarkable capacity retention ratio of 95.4 % after 100cycles at 2.0C and room temperature, and outstanding reversible discharge specific capacity of 148.2 mAh g-1 at 5.0C. Even under elevated temperature of 60 °C, it delivers excellent capacity retention ratio of 92.2 % after 100cycles at 2.0C, which is significantly superior to the 47.9 % of the unmodified cathode material. Thus, the in-situ Ti4+-doped strategy presents superior advantages in enhancing the structural stability of Ni-rich cathode materials for LIBs.

Metal π-Lewis base activation in palladium(0)-catalyzed trans-alkylative cyclization of alkynals.

The Pd(0)-mediated umpolung reaction of an alkyne to achieve trans-difunctionalization is a potential synthetic methodology, but its insightful activation mechanism of Pd(0)-alkyne interaction has yet to be established. Here, a Pd(0)-π-Lewis base activation mode is proposed and investigated by combining theoretical and experimental studies. In this activation mode, the Pd(0) coordinates to the alkyne group and enhances its nucleophilicity through π-back-donation, facilitating the nucleophilic attack on the aldehyde to generate a trans-Pd(ii)-vinyl complex. Ligand-effect studies reveal that the more electron-donating one would accelerate the reaction, and the cyclization of the challenging flexible C- or O-tethered substrates has been realized. The origin of regioselectivities is also explicated by the newly proposed metal π-Lewis base activation mode.

Postoperative urinary retention following transanal versus laparoscopic total mesorectal excision for rectal cancer: A randomized trial report from an experienced center.

Background: Transanal total mesorectal excision has emerged as a potential solution to certain limitations associated with laparoscopic total mesorectal excision in rectal cancer patients. Differences in surgical approaches have raised questions regarding their impact on the risk of postoperative urinary retention, with limited data available from large scale randomized clinical study. Objective: To report incidence of postoperative urinary retention and evaluate the associated risk factors for transanal total mesorectal excision. Design: In this randomized controlled trial (ClinicalTrials. gov NCT06147492), we retrieved 524 patients who received total mesorectal excision (TME) for stage I-III rectal cancer between June 2019 and April 2022, and the patients were randomly assigned in a 1:1 ratio to undergo either taTME or laTME. Patients: We enrolled 524 patients who underwent total mesorectal excision for stage I-III rectal cancer between June 2019 and April 2022. Main outcome measures: The incidence of postoperative urinary retention. Results: Among the 524 enrolled patients, 261 were randomized to the laTME group, while 263 were were randomized the taTME group. The median age was 58 years, and 340 participants (64.8 %) were male. Notably, 37 individuals (7.0 %) experienced postoperative urinary retention during the follow-up period, with no significant disparity was observed between the taTME and laTME groups (6.8 % and 7.2 %, respectively, P = 0.98). Risk factors associated with PUR in patients following taTME encompassed early removal of the urinary catheter (P = 0.006), net infusion rate >4.09 ml kg-1.h-1 (P = 0.006), and an age surpassing 65 years (P = 0.0321). Limitations: The generalizability of the findings outside specialist rectal cancer centers may be limited. Conclusions: Transanal total mesorectal excision was not found to heighten the risk of postoperative urinary retention. Nonetheless, it is advisable removing postoperative catheter beyond the initial day and exercising caution in the administration of intravenous fluids in clinical practice for taTME procedures.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Drug sensitivity testing during dental pulp-dentin complex repair: its effect on treatment outcome and prognosis.

OBJECTIVE: To assess the efficacy of targeted therapy based on drug sensitivity testing (DST) results in patients with acute pulpitis (AP). METHODS: A total of 80 cases of AP were included retrospectively and divided into two groups: control (Ctrl) group (conventional drug palliative therapy, n=40) and experimental (Exp) group (DST + non-resistant drugs, n=40). The clinical data and laboratory examination data of patients, including bacterial culture data, drug sensitivity test results, Ca and P contents in dental pulp, visual analogue scale (AVS), treatment satisfaction, and dental pulp incidence, were collected and analyzed. RESULTS: Prevotella melaninogenica, Fusobacterium nucleatum, and Porphyromonas gingivalis exhibited higher resistance rates (RS) to penicillin and amoxicillin but no resistance to imipenem and metronidazole. The content of Ca and P in the dental pulp of the Exp group patients was significantly higher than that of the Ctrl group (P=0.006). The total response rate (95% vs. 77.5%, P=0.018) and overall patient satisfaction (92.5% vs. 80%, P=0.021) were also significantly higher in the Exp group than in the Ctrl group. Additionally, when the follow-up duration exceeded 1 year, the incidence of dental pulp reactions in the Exp group was significantly lower than that of the Ctrl group (P=0.026). CONCLUSIONS: These findings suggest that Gram-negative anaerobes are the predominant oral pathogens in patients with AP. Imipenem and metronidazole demonstrate the most effective anti-infective properties against these anaerobes. Utilizing DST to select non-resistant drugs for treatment prior to therapy effectively enhances clinical outcomes for patients with AP.

A Small "Tent" in the Esophagus.

Cite this article as: Zong Z, Xu J, Zhang H, Xu H, Tang X, Shi L. A small "tent" in the esophagus. Turk J Gastroenterol. 2024;35(7): 587-588.

Rheumatoid arthritis complicated with cervical actinomycosis and ureteral obstruction: A case report and literature review. / ç±»é£Žæ¹¿å ³èŠ‚ç‚Žåˆå¹¶å®«é¢ˆæ”¾çº¿èŒç— åŠè¾“å°¿ç®¡æ¢—é˜»1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts, often misdiagnosed due to its similarity to many infectious and non-infectious diseases. This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics, including methotrexate, leflunomide, and infliximab, leading to recurrent joint pain, poorly controlled rheumatoid arthritis activity, and persistent elevation of white blood cell counts. Abdominal CT revealed a pelvic mass and right ureteral dilation. Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules, indicating actinomycosis. The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide, hydroxychloroquine sulfate, and tofacitinib, resulting in improved joint symptoms and normalized white blood cell counts. After 2 years of follow-up, the patient remained stable with no recurrence. This case highlights the importance of clinicians being vigilant for infections, particularly chronic, occult infections from rare pathogens, in rheumatoid arthritis patients on potent immunosuppressants and biologics, advocating for early screening and diagnosis.

Single-cell transcriptomics reveals writers of RNA modification-mediated immune microenvironment and cardiac resident Macro-MYL2 macrophages in heart failure.

BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

Natural killer cell-associated prognosis model characterizes immune landscape and treatment efficacy of diffuse large B cell lymphoma.

PURPOSE: NK cells are essential for the detection, identification and prediction of cancer. However, so far, there is no prognostic risk model based on NK cell-related genes to predict the prognosis and treatment outcome of DLBCL patients. This study aimed to explore a risk assessment model that could accurately predict the prognosis and treatment efficacy of DLBCL. METHODS: Bioinformatics analysis of the expression profiles of DLBCL samples in the GEO database was performed. Cox regression and LASSO regression analysis were used to determine NK cell-related genes associated with patient's prognosis. Based on these genes, a risk assessment model was constructed to predict the prognosis of patients and the effectiveness of treatment. Finally, qRT-PCR was used to verify the expression of gene tags in clinical samples. RESULTS: We identified seven prognosis-related NK cell-related genes (MAP2K1, PRKCB, TNFRSF10B, IL18, LAMP1, RASGRP1, and SP110), and DLBCL patients were divided into low- and high-risk groups based on these genes. Survival analysis showed that the prognosis of patients with low-risk group was better. Pathway enrichment analysis showed that the differentially expressed genes between the two risk groups were related to immune response pathways. Compared with the high-risk group, the low-risk group had higher infiltration of immune cells in tumor tissues. Besides, compared with high-risk group, low-risk patients by immunotherapy or other commonly used anti-tumor drugs might have better efficacy after treatment. In addition, qRT-PCR showed that the expression of risk genes including TNFRSF10B, IL18 and LAMP1 were significantly increased in most DLBCL samples compared to control samples, while the expression of protective genes including MAP2K1, PRKCB, RASGRP1 and SP110 were significantly decreased. CONCLUSION: The NK cell-related gene signatures were proved to be a reliable indicator of the success of immunotherapy in patients with DLBCL, thus providing a unique evaluation method.

Well-balanced performance achieved in PZT piezoceramics via a multiscale regulation strategy.

Emerging high-power piezoelectric applications demand the development of piezoelectric materials featuring both a high mechanical quality factor (Qm) and a large piezoelectric coefficient (d33). However, it is widely accepted that an increase in d33 is usually accompanied with a decrease in Qm, and vice versa. Herein, a multiscale regulation strategy is proposed to improve Qm and d33 simultaneously from the perspectives of phase structure, ferroelectric domains, and lattice defects. A well-balanced combination of electromechanical performances with Qm = 726, d33 = 502 pC N-1, kp = 0.69, tan δ = 0.0024, and TC = 267 °C was obtained. Through structural characterization, it was observed that the morphotropic phase boundary and enhanced dispersion behavior lead to a lowered energy barrier, which contributes to polarization rotation and enhances piezoelectric performance. At the same time, the excellent piezoelectric performances also benefit from the highly oriented domain structure and small domain size after high-temperature poling. Furthermore, the segregation of Ba2+ causes A-site defects in the crystal lattice, accompanied with an increase in oxygen vacancies, which maintains the hardening effect of the ceramics. This study proposes a multiscale regulation strategy, providing insights for the design of high-power piezoelectric ceramics with high d33 and Qm.

Multiple-model based simulation of urban atmospheric methane concentration and the attributions to its seasonal variations: A case study in Hangzhou megacity, China.

Cities are treated as global methane (CH4) emission hotspots and the monitoring of atmospheric CH4 concentration in cities is necessary to evaluate anthropogenic CH4 emissions. However, the continuous and in-situ observation sites within cities are still sparsely distributed in the largest CH4 emitter as of China, and although obvious seasonal variations of atmospheric CH4 concentrations have been observed in cities worldwide, questions regarding the drivers for their temporal variations still have not been well addressed. Therefore, to quantify the contributions to seasonal variations of atmospheric CH4 concentrations, year-round CH4 concentration observations from 1st December 2020 to 30th November 2021 were conducted in Hangzhou megacity, China, and three models were chosen to simulate urban atmospheric CH4 concentration and partition its drivers including machine learning based Random Forest (RF) model, atmospheric transport processes based numerical model (WRF-STILT), and regression analysis based Multiple Linear Regression (MLR) model. The findings are as follows: (1) the atmospheric CH4 concentration showed obvious seasonal variations and were different with previous observations in other cities, the seasonality were 5.8 ppb, 21.1 ppb, and 50.1 ppb between spring-winter, summer-winter and autumn-winter, respectively, where the CH4 background contributed by -8.1 ppb, -44.6 ppb, and -1.0 ppb, respectively, and the CH4 enhancements contributed by 13.9 ppb, 65.7 ppb, and 51.1 ppb. (2) The RF model showed the highest accuracy in simulating CH4 concentrations, followed by MLR model and WRF-STILT model. (3) We further partition contributions from different factors, results showed the largest contribution was from temperature-induced increase in microbial process based CH4 emissions including waste treatment and wetland, which ranged from 38.1 to 76.3 ppb when comparing different seasons with winter. The second largest contribution was from seasonal boundary layer height (BLH) variations, which ranged from -13.4 to -6.3 ppb. And the temperature induced seasonal CH4 emission and enhancement variations were overwhelming BLH changes and other meteorological parameters.

Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

The biogenesis and transport of triglyceride-rich lipoproteins.

Triglyceride-rich lipoproteins (TRLs) play essential roles in human health and disease by transporting bulk lipids into the circulation. This review summarizes the fundamental mechanisms and diverse factors governing lipoprotein production, secretion, and regulation. Emphasizing the broader implications for human health, we outline the intricate landscape of lipoprotein research and highlight the potential coordination between the biogenesis and transport of TRLs in physiology, particularly the unexpected coupling of metabolic enzymes and transport machineries. Challenges and opportunities in lipoprotein biology with respect to inherited diseases and viral infections are also discussed. Further characterization of the biogenesis and transport of TRLs will advance both basic research in lipid biology and translational medicine for metabolic diseases.