Temporal control in shell-core structured nanofilm for tracheal cartilage regeneration: synergistic optimization of anti-inflammation and chondrogenesis.

Cartilage tissue engineering offers hope for tracheal cartilage defect repair. Establishing an anti-inflammatory microenvironment stands as a prerequisite for successful tracheal cartilage restoration, especially in immunocompetent animals. Hence, scaffolds inducing an anti-inflammatory response before chondrogenesis are crucial for effectively addressing tracheal cartilage defects. Herein, we develop a shell-core structured PLGA@ICA-GT@KGN nanofilm using poly(lactic-co-glycolic acid) (PLGA) and icariin (ICA, an anti-inflammatory drug) as the shell layer and gelatin (GT) and kartogenin (KGN, a chondrogenic factor) as the core via coaxial electrospinning technology. The resultant PLGA@ICA-GT@KGN nanofilm exhibited a characteristic fibrous structure and demonstrated high biocompatibility. Notably, it showcased sustained release characteristics, releasing ICA within the initial 0 to 15 days and gradually releasing KGN between 11 and 29 days. Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released ICA from the shell layer, while the KGN released from the core layer effectively induced chondrogenic differentiation of bone marrow stem cells (BMSCs). Following this, the synthesized PLGA@ICA-GT@KGN nanofilms were loaded with BMSCs and stacked layer by layer, adhering to a 'sandwich model' to form a composite sandwich construct. This construct was then utilized to repair circular tracheal defects in a rabbit model. The sequential release of ICA and KGN facilitated by the PLGA@ICA-GT@KGN nanofilm established an anti-inflammatory microenvironment before initiating chondrogenic induction, leading to effective tracheal cartilage restoration. This study underscores the significance of shell-core structured nanofilms in temporally regulating anti-inflammation and chondrogenesis. This approach offers a novel perspective for addressing tracheal cartilage defects, potentially revolutionizing their treatment methodologies.

SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway.

Lung cancer (LC) is the leading cause of cancer-associated deaths worldwide, among which non-small-cell lung cancer (NSCLC) accounts for 80%. Stromal cell-derived factor-1 (SDF-1) inhibition results in a significant depletion of NSCLC metastasis. Additionally, SDF-1 is the only natural chemokine known to bind and activate the receptor CXCR4. Thus, we attempted to clarify the molecular mechanism of SDF-1 underlying NSCLC progression. Transwell migration, adhesion, and G-LISA assays were used to assess megakaryocytic chemotaxis in vitro and in vivo in terms of megakaryocytic migration, adherence, and RhoA activation, respectively. Western blotting was used to assess PI3K/Akt-associated protein abundances in MEG-01 cells and primary megakaryocytes under the indicated treatment. A hematology analyzer and flow cytometry were used to assess platelet counts in peripheral blood and newly formed platelet counts in Lewis LC mice under different treatments. Immunochemistry and flow cytometry were used to measure CD41+ megakaryocyte numbers in Lewis LC mouse tissue under different treatments. ELISA was used to measure serum TPO levels, and H&E staining was used to detect NSCLC metastasis.SDF-1 receptor knockdown suppressed megakaryocytic chemotaxis in Lewis LC mice. SDF-1 receptor inhibition suppressed megakaryocytic chemotaxis via the PI3K/Akt pathway. SDF-1 receptor knockdown suppressed CD41+ megakaryocyte numbers in vivo through PI3K/Akt signaling. SDF-1 receptor inhibition suppressed CD41+ megakaryocytes to hinder NSCLC metastasis. SDF-1 facilitates NSCLC metastasis by enhancing the chemoattraction of megakaryocytes via the PI3K/Akt signaling pathway, which may provide a potential new direction for seeking therapeutic plans for NSCLC.

Efficacy and safety of Trastuzumab Emtansine in treating human epidermal growth factor receptor 2-positive metastatic breast cancer in Chinese population: a real-world multicenter study.

Background: Trastuzumab emtansine (T-DM1) has been approved worldwide for treating metastatic breast cancer (mBC) in patients who have received first-line therapy, shown disease progression, and are human epidermal growth factor receptor 2 (HER2)-positive. T-DM1 received approval in China to treat early-stage breast cancer (BC) in 2020 and for mBC in 2021. In March 2023, T-DM1 was included in medical insurance coverage, significantly expanding the eligible population. Materials and methods: This post-marketing observational study aimed to assess the safety and effectiveness of T-DM1 in real-world clinical practice in China. This study enrolled 31 individuals with HER2-positive early-stage BC and 70 individuals with HER2-positive advanced BC from 8 study centers in Shandong Province, China. The T-DM1 dosage was 3.6 mg/kg injected intravenously every 3 weeks until the disease advanced or the drug toxicity became uncontrollable, whichever occurred earlier. Additionally, efficacy and safety information on T-DM1 were collected. Results: During the 7-month follow-up period, no recurrence or metastases were observed in patients who had early-stage BC. The disease control rate was 31.43% (22/70) in patients with advanced BC. The most common adverse effect of T-DM1 was thrombocytopenia, with an incidence of 69.31% (70/101), and the probability of Grade ≥ 3 thrombocytopenia was 11.88% (12/101). Conclusion: This real-world study demonstrated that T-DM1 had good efficacy and was well tolerated by both HER2-positive early-stage BC and mBC patients.

TiN/anatase/rutile phase junction obtained by in-situ thermal transformation for efficient photothermal-assisted photocatalytic hydrogen generation.

Phase junctions exhibit great potential in photocatalytic energy conversion, yet the narrow light response region and inefficient charge transfer limit their photocatalytic performance. Herein, an anatase/rutile phase junction modified by plasmonic TiN and oxygen vacancies (TiN/(A-R-TiO2-Ov)) is prepared through an in-situ thermal transformation from TiN for efficient photothermal-assisted photocatalytic hydrogen production for the first time. The content of TiN, oxygen vacancies, and phase components in TiN/(A-R-TiO2-Ov) hybrids can be well-adjusted by tuning the heating time. The as-prepared photocatalysts display a large specific area and wide light absorption due to the synergistic effect of plasmonic excitation, oxygen vacancies, and bandgap excitations. Meanwhile, the multi-interfaces between TiN, anatase, and rutile provide built-in electric fields for efficient separation of photoinduced carriers and hot electron injection via ohmic contact and type-Ⅱ band arrangement. As a result, the TiN/(A-R-TiO2-Ov) photocatalyst shows an excellent photocatalytic hydrogen generation rate of 15.07 mmol/g/h, which is 20.6 times higher than that of titanium dioxide P25. Moreover, temperature-dependent photocatalytic tests reveal that the excellent photothermal conversion caused by plasmonic heating and crystal lattice vibrations in TiN/(A-R-TiO2-Ov) has about 25 % enhancement in photocatalysis (18.84 mmol/g/h). This work provides new inspiration for developing high-performance photocatalysts by optimizing charge transfer and photothermal conversion.

Metabolomics analysis of different diameter classes of Taxus chinensis reveals that the resource allocation is related to carbon and nitrogen metabolism.

Taxus chinensis (Taxus cuspidata Sieb. et Zucc.) is a traditional medicinal plant known for its anticancer substance paclitaxel, and its growth age is also an important factor affecting its medicinal value. However, how age affects the physiological and metabolic characteristics and active substances of T. chinensis is still unclear. In this study, carbon and nitrogen accumulation, contents of active substances and changes in primary metabolites in barks and annual leaves of T. chinensis of different diameter classes were investigated by using diameter classes instead of age. The results showed that leaves and barks of small diameter class (D1) had higher content of non-structural carbohydrates and C, which were effective in enhancing defense capacity, while N content was higher in medium (D2) and large diameter classes (D3). Active substances such as paclitaxel, baccatin III and cephalomannine also accumulated significantly in barks of large diameter classes. Moreover, 21 and 25 differential metabolites were identified in leaves and barks of different diameter classes, respectively. The differential metabolites were enhanced the TCA cycle and amino acid biosynthesis, accumulate metabolites such as organic acids, and promote the synthesis and accumulation of active substances such as paclitaxel in the medium and large diameter classes. These results revealed the carbon and nitrogen allocation mechanism of different diameter classes of T. chinensis, and its relationship with medicinal components, providing a guidance for the harvesting and utilization of wild T. chinensis.

PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.

Metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion/Caco-2 cell transport, and their prebiotic effects during colonic fermentation.

The health-promoting activities of polyphenols and their metabolites originating from germinated quinoa (GQ) are closely related to their digestive behavior, absorption, and colonic fermentation; however, limited knowledge regarding these properties hinder further development. The aim of this study was to provide metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion and Caco-2 cell transport, whilst also investigating the changes in the major polyphenol metabolites and the effects of prebiotics during colonic fermentation. It was found that germination treatment increased the polyphenol content of quinoa by 21.91%. Compared with RQ group, 23 phenolic differential metabolites were upregulated and 47 phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after simulated digestion, 7 kinds of phenolic differential metabolites were upregulated and 17 kinds of phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after cell transport, 7 kinds of phenolic differential metabolites were upregulated and 9 kinds of phenolic differential metabolites were downregulated in GQ group. In addition, GQ improved the bioaccessibilities and transport rates of various polyphenol metabolites. During colonic fermentation, GQ group can also increase the content of SCFAs, reduce pH value, and adjust gut microbial populations by increasing the abundance of Actinobacteria, Bacteroidetes, Verrucomicrobiota, and Spirochaeota at the phylum level, as well as Bifidobacterium, Megamonas, Bifidobacterium, Brevundimonas, and Bacteroides at the genus level. Furthermore, the GQ have significantly inhibited the activity of α-amylase and α-glucosidase. Based on these results, it was possible to elucidate the underlying mechanisms of polyphenol metabolism in GQ and highlight its beneficial effects on the gut microbiota.

Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Molecular characterization, clinical value, and cancer-immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer.

BACKGROUND: This research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC). METHODS: The data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool. RESULTS: SRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib. CONCLUSION: In conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Discovery of an immunosuppressive functional metabolite from the insect-derived endophytic Aspergillus taichungensis SMU01.

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

USP15 promotes the progression of papillary thyroid cancer by regulating HMGB1 stability through its deubiquitination.

Purpose: Papillary thyroid cancer (PTC) stands as one of the most prevalent types of thyroid cancers, characterized by a propensity for in-situ recurrence and distant metastasis. The high mobility group protein (HMGB1), a conserved nuclear protein, plays a pivotal role in carcinogenesis by stimulating tumor cell growth and migration. Nevertheless, the underlying mechanism driving aberrant HMGB1 expression in PTC necessitates further elucidation. Materials and methods: Our study unraveled the impact of low and overexpression of USP15 on the proliferation, invasion, and metastasis of PTC cells. Through a comprehensive array of molecular techniques, we uncovered the intricate relationship between HMGB1 and USP15 in the progression of PTC. Results: In this study, we identified USP15, a deubiquitinase in the ubiquitin-specific proteases family, as a true deubiquitylase of HMGB1 in PTC. USP15 was shown to interact with HMGB1 in a deubiquitination activity-dependent manner, deubiquitinating and stabilizing HMGB1. USP15 depletion significantly decreased PTC cell proliferation, migration, and invasion. In addition, the effects induced by USP15 depletion could be rescued by further HMGB1 overexpression. But when HMGB1 is knocked down, even overexpression of USP15 could not promote the progression of PTC cells. Conclusion: In essence, our discoveries shed light on the previously uncharted catalytic role of USP15 as a deubiquitinating enzyme targeting HMGB1, offering a promising avenue for potential therapeutic interventions in the management of PTC.

Intestinal microbiota via NLRP3 inflammasome dependent neuronal pyroptosis mediates anxiety-like behaviour in mice exposed to 3.5 GHz radiofrequency radiation.

The rapid development of 5G communication technology has increased public concern about the potential adverse effects on human health. Till now, the impacts of radiofrequency radiation (RFR) from 5G communication on the central nervous system and gut-brain axis are still unclear. Therefore, we investigated the effects of 3.5 GHz (a frequency commonly used in 5G communication) RFR on neurobehavior, gut microbiota, and gut-brain axis metabolites in mice. The results showed that exposure to 3.5 GHz RFR at 50 W/m2 for 1 h over 35 d induced anxiety-like behaviour in mice, accompanied by NLRP3-dependent neuronal pyroptosis in CA3 region of the dorsal hippocampus. In addition, the microbial composition was widely divergent between the sham and RFR groups. 3.5 GHz RFR also caused changes in metabolites of feces, serum, and brain. The differential metabolites were mainly enriched in glycerophospholipid metabolism, tryptophan metabolism, and arginine biosynthesis. Further correlation analysis showed that gut microbiota dysbiosis was associated with differential metabolites. Based on the above results, we speculate that dysfunctional intestinal flora and metabolites may be involved in RFR-induced anxiety-like behaviour in mice through neuronal pyroptosis in the brain. The findings provide novel insights into the mechanism of 5G RFR-induced neurotoxicity.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.

Is fracture management merely a physical process? Exploring the psychological effects of internal and external fixation.

BACKGROUND: Internal and external fixation are common surgical procedures for treating fractures. However, the impact of different surgical approaches (including internal and external fixations) on patients' psychological status and Quality of Life (QoL) is rarely examined. Herein, we aimed to investigate the effects of internal and external fixation on anxiety, depression, insomnia, and overall mental and physical health in Distal Radius Fractures (DRF) patients. METHODS: We performed a retrospective study on 96 fracture patients who underwent internal fixation (57 patients) or external fixation (39 patients). The Visual Analog Scale (VAS), the Hospital Anxiety and Depression Scale (HADS), the Athens Insomnia Scale (AIS), and the Medical Outcomes Study Short Form 36 (SF-36) questionnaire were used to assess the patients' pain, anxiety, depression, sleep, and QoL before surgery and at seven days, one month, and three months post-surgery. RESULTS: The VAS scores were significantly lower in the Internal Fixation Group (IFG) than in the External Fixation Group (EFG) on the seventh day and one month postoperatively (P < 0.05). Although both groups showed no significant anxiety, depression, or insomnia before surgery (P > 0.05), the EFG showed significantly higher HADS-A, HADS-D, and AIS scores than the IFG at seven days and one and three months postoperatively (P < 0.05). Additionally, changes in HADS-A, HADS-D, and AIS scores were most significant at day seven post-surgery in the EFG (P < 0.05). Furthermore, no significant difference was found between the two groups in the average Physical Component Summary (PCS) and Mental Component Summary (MCS) scores before surgery (P > 0.05). However, both groups showed positive changes in PCS and MCS scores at postoperative day seven and one and three months postoperatively, with the IFG having significantly higher average PCS and MCS scores compared to the EFG (P < 0.05). CONCLUSION: Compared to external fixation, internal fixation did not significantly impact patients' emotions regarding anxiety and depression in the early postoperative period, and physical and mental health recovery was better during the postoperative rehabilitation period. Furthermore, when there are no absolute indications, the impact on patients' psychological well-being should be considered as one of the key factors in the treatment plan during surgical approach selection.

Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study.

Background: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China. Methods: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson χ2 test and Mann-Whitney test were performed to analyze the differences among variables. Results: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year. Conclusions: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

Hereditary hemochromatosis caused by a C282Y/H63D mutation in the HFE gene: A case report.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Electrochemical Generation of Te Vacancy Pairs in PtTe for Efficient Hydrogen Evolution.

Two-dimensional (2D) van der Waals materials are increasingly seen as potential catalysts due to their unique structures and unmatched properties. However, achieving precise synthesis of these remarkable materials and regulating their atomic and electronic structures at the most fundamental level to enhance their catalytic performance remain a significant challenge. In this study, we synthesized single-crystal bulk PtTe crystals via chemical vapor transport and subsequently produced atomically thin, large PtTe nanosheets (NSs) through electrochemical cathode intercalation. These NSs are characterized by a significant presence of Te vacancy pairs, leading to undercoordinated Pt atoms on their basal planes. Experimental and theoretical studies together reveal that Te vacancy pairs effectively optimize and enhance the electronic properties (such as charge distribution, density of states near the Fermi level, and d-band center) of the resultant undercoordinated Pt atoms. This optimization results in a significantly higher percentage of dangling O-H water, a decreased energy barrier for water dissociation, and an increased binding affinity of these Pt atoms to active hydrogen intermediates. Consequently, PtTe NSs featuring exposed and undercoordinated Pt atoms demonstrate outstanding electrocatalytic activity in hydrogen evolution reactions, significantly surpassing the performance of standard commercial Pt/C catalysts.

[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.