Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8+ T cells.

Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer cells may preferentially rely on certain amino acids for rapid growth and metastasis. On the other hand, sufficient nutrient availability and uptake are necessary for mounting an effective T cell anti-tumor response in the tumor microenvironment (TME). Here we demonstrate that tumor cells outcompete T cells for cystine uptake due to high Slc7a11 expression. This competition induces T-cell exhaustion and ferroptosis, characterized by diminished memory formation and cytokine secretion, increased PD-1 and TIM-3 expression, as well as intracellular oxidative stress and lipid-peroxide accumulation. Importantly, either Slc7a11 deletion in tumor cells or intratumoral cystine supplementation improves T cell anti-tumor immunity. Mechanistically, cystine deprivation in T cells disrupts glutathione synthesis, but promotes CD36 mediated lipid uptake due to dysregulated cystine/glutamate exchange. Moreover, enforced expression of glutamate-cysteine ligase catalytic subunit (Gclc) promotes glutathione synthesis and prevents CD36 upregulation, thus boosting T cell anti-tumor immunity. Our findings reveal cystine as an intracellular metabolic checkpoint that orchestrates T-cell survival and differentiation, and highlight Gclc as a potential therapeutic target for enhancing T cell anti-tumor function.

Effectiveness of musculoskeletal manipulations in patients with neck pain: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Neck pain is a common problem that severely affects physical and mental health. While musculoskeletal manipulations are recommended as the first-line treatment for adults with neck pain, the comparative effectiveness of different musculoskeletal manipulations remains unclear. This systematic review and network meta-analysis of randomised controlled trials (RCTs) will compare the effectiveness of different types of musculoskeletal manipulations, with the overarching aim of guiding clinical practice. METHODS AND ANALYSIS: Two independent reviewers will search four English electronic databases (Web of Science, Cochrane Library, EMBASE, PubMed) and three Chinese electronic databases (China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang) for relevant RCTs published from 1 January 2013 to 30 April 2023. The Clinical Trials Registry (ClinicalTrials.gov) will be searched for completed but unpublished RCTs. English and Chinese will be used to search English databases and Chinese databases, respectively. RCTs of musculoskeletal manipulations for adults (aged ≥18 years) with neck pain will be considered eligible for inclusion. A pairwise meta-analysis and network meta-analysis will be performed, and pooled risk ratios, standardised mean differences and 95% CIs will be determined. ETHICS AND DISSEMINATION: Ethics approval is not required as this study is a literature review. The results of this review will be published in peer-reviewed journals or disseminated at conferences. PROSPERO REGISTRATION NUMBER: CRD42023420775.

Mussel-inspired near-infrared light-responsive gelatin-based hydrogels for enhancing MRSA-infected wound healing.

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.

Vitamin D delays intervertebral disc degeneration and improves bone quality in ovariectomized rats.

Known to be involved in bone-cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague-Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6-month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX-induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD.

Interaction of estradiol and vitamin D with low skeletal muscle mass among middle-aged and elderly women.

BACKGROUND: Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together. METHODS: Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer. Bivariate logistic regression and multiplicative interaction analyses were used to assess the impact of estradiol level and vitamin D status on low SMM, as well as the combined impact of estradiol and low vitamin D status on low SMM. RESULTS: A total of 287 (9.49%) participants had low SMM, which had lower levels of estradiol and vitamin D concentration than normal SMM group. While, after adjusting the confounding variables, these correlations were maintained in estradiol Q1, Q2, Q3 and vitamin D Q1. Furthermore, the significant combined effect of the highest quartile of estradiol concentrations and non-vitamin D deficiency, and interactions between vitamin D Q1 and estradiol Q2, vitamin D Q1 and estradiol Q3, vitamin D Q2 and estradiol Q1, vitamin D Q3 and estradiol Q3 on low SMM were stably reflected (P for interaction < 0.05). CONCLUSIONS: Estradiol and vitamin D were interrelated with low SMM in middle-aged and elderly women. Combination of estradiol and vitamin D supplements should be encouraged for middle-aged and elderly women who are at risk of muscle atrophy or experiencing muscle atrophy.

α-Ketoglutaric acid ameliorates intervertebral disk degeneration by blocking the IL-6/JAK2/STAT3 pathway.

Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1ß-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1ß-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway.

Bibliometric Analysis of Research Trends on Tuina Manipulation for Neck Pain Treatment Over the Past 10 Years.

Tuina is an effective treatment for neck pain (NP). However, there has been no bibliometric analysis of the global application and emerging trends of tuina performed for NP. Therefore, this study aimed to provide an overview of the current state and future trends in the field. Articles about tuina for NP, published from January 1, 2013, to January 1, 2023, were searched in the Web of Science Core Collection database. CiteSpace (6.1.R6) and VOSviewer (1.6.18) software were used to analyze annual trends in literature posts, countries, institutions, authors, cited references, and knowledge graphs of keyword co-occurrence, clustering, and burst using standard bibliometric indicators. The final analysis comprised 505 valid documents. The results demonstrate that the number of articles in the field of tuina therapy for NP has gradually increased over the years, showing the most active countries, institutions, journals, and authors. There were 323 keywords in the field, 322 research authors, and 292 research institutions, with the USA having the most publications (n = 140). The most published institution is Vrije University Amsterdam, and the most published journal is the Cochrane Database of Systematic Reviews. Peter R Blanpied is the most influential and most-cited author. Interventions (dry needling, massage therapy, and muscle energy techniques), common treatment sites for NP (upper trapezius), and complications (cervicogenic headache) are the top three frontiers mentioned in the field of tuina research for NP. The bibliometric study showed the current status and trends in clinical research on treating patients with NP using tuina, which may help researchers identify topics of interest and scope for future research in this field.

Colloidal bismuth pectin-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection: A multicenter, randomized, double-blind, non-inferiority clinical trial.

BACKGROUND: Bismuth-containing quadruple therapy is an effective regimen for Helicobacter pylori (H. pylori) treatment. No head-to-head comparison trials have been conducted to evaluate the efficacy of colloidal bismuth pectin (CBP) in quadruple therapy for eradicating H. pylori. We aimed to compare the efficacy and safety of CBP quadruple therapy and bismuth potassium citrate (BPC) quadruple therapy for 14 days in the first-line treatment of H. pylori. METHODS: In this multicenter, randomized, double-blind, non-inferiority clinical trial, H. pylori-infected subjects without eradication history were randomized to receive amoxicillin 1 g twice daily, tetracycline 500 mg three time daily, esomeprazole 20 mg twice daily in combination with CBP 200 mg three time daily or BPC 240 mg twice daily for 14 days. 13 C-urea breath tests were used to access the eradication rate at least 4 weeks after treatment. RESULTS: Between April 2021 and July 2022, 406 patients were assessed for eligibility and 339 subjects were randomized. The cure rates (primary outcome) of CBP and BPC quadruple therapy were 90.5% and 92.3% (p = 0.56) by intention-to-treat analysis, respectively, and 96.1% and 96.2% (p = 1.00) by per-protocol analysis, respectively. CBP quadruple therapy was non-inferior to BPC quadruple therapy in the intention-to-treat and per-protocol analysis (p < 0.025). The frequency of adverse events and compliance were not different among the two groups (p > 0.05). CONCLUSIONS: Both CBP and BPC quadruple therapy for 14 days provide high efficacy, good compliance, and safety in the first-line treatment of H. pylori in China.

Artificial intelligence-based multi-omics analysis fuels cancer precision medicine.

With biotechnological advancements, innovative omics technologies are constantly emerging that have enabled researchers to access multi-layer information from the genome, epigenome, transcriptome, proteome, metabolome, and more. A wealth of omics technologies, including bulk and single-cell omics approaches, have empowered to characterize different molecular layers at unprecedented scale and resolution, providing a holistic view of tumor behavior. Multi-omics analysis allows systematic interrogation of various molecular information at each biological layer while posing tricky challenges regarding how to extract valuable insights from the exponentially increasing amount of multi-omics data. Therefore, efficient algorithms are needed to reduce the dimensionality of the data while simultaneously dissecting the mysteries behind the complex biological processes of cancer. Artificial intelligence has demonstrated the ability to analyze complementary multi-modal data streams within the oncology realm. The coincident development of multi-omics technologies and artificial intelligence algorithms has fuelled the development of cancer precision medicine. Here, we present state-of-the-art omics technologies and outline a roadmap of multi-omics integration analysis using an artificial intelligence strategy. The advances made using artificial intelligence-based multi-omics approaches are described, especially concerning early cancer screening, diagnosis, response assessment, and prognosis prediction. Finally, we discuss the challenges faced in multi-omics analysis, along with tentative future trends in this field. With the increasing application of artificial intelligence in multi-omics analysis, we anticipate a shifting paradigm in precision medicine becoming driven by artificial intelligence-based multi-omics technologies.

Effects of maternal supplementation of fish oil during late gestation and lactation on growth performance, fecal microbiota structure and post-weaning diarrhoea of offspring piglets.

Homeostasis of gut microbiota is a critical contributor to growth and health in weaned piglets. Fish oil is widely reported to benefit health of mammals including preventing intestinal dysfunction, yet its protective effect during suckling-to-weaning transition in piglets remains undetermined. Low (30 g/d) and high (60 g/d) doses of n-3-rich fish oil were supplemented in sows from late gestation to lactation. Serum indicators and gut microbiota were determined to evaluate the effects of maternal fish oil on growth performance, immunity and diarrhea of piglets. DHA and EPA in the colostrum as well as serum of suckling and 1-week post-wean piglets were significantly and linearly increased by maternal supplementation of fish oil (P < 0.05). IGF1 and T3 in nursing and weaned piglets were significantly elevated by maternal fish oil (P < 0.05), and the increase of IGF1 was concerning the dosage of fish oil. Colostrum IgG, plasma IgG, IgM in suckling piglets, IgG, IgM and IgA in weaned piglets were significantly increase as maternal replenishment of fish oil increased (P < 0.05). Additionally, cortisol was significantly reduced in weaned pigs (P < 0.05), regardless of dosage. 16S rRNA sequencing revealed that α-diversity of fecal microbiota in nursery piglets, and fecal Lactobacillus genus, positively correlated with post-weaning IgA, was significantly increased by high dosage. Collectively, maternal fish oil during late pregnancy and lactation significantly promoted growth, enhanced immunity, and reduced post-weaning diarrhea in piglets, therefore facilitated suckling-to-weaning transition in piglets, which may be partially due to the altered gut microbial community.

Stereoselective effects of chiral epoxiconazole on the metabolomic and lipidomic profiling of leek.

Epoxiconazole is widely used in agriculture to control plant diseases; however, its effect on the nutritional quality of crops is poorly understood. In the present study, the stereoselective effects of epoxiconazole and its enantiomers on leek metabolites and lipids were clarified using metabolomics and lipidomics based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Multivariate analysis revealed significant differences in 123 compounds of leek exposed to chiral epoxiconazole compared to the control group. The order of the degree of influence was (+)-epoxiconazole > racemic-epoxiconazole>(-)-epoxiconazole, indicating significant stereoselectivity. The differential expression of metabolites indicated the activation of stress defense systems, including the antioxidant defense system and signaling pathways and phenylpropanoid metabolism. Alterations in the levels of compounds associated with nutritional quality, such as amino acids, vitamins, phenylpropanoids, flavonoids and lipids indicated changes in the nutritional quality of leek. In general, the nutritional quality of leek decreased after exposure to epoxiconazole.

Application of photo-responsive metal-organic framework in cancer therapy and bioimaging.

Metal-organic frameworks (MOFs) are a class of hybrid porous crystalline materials that are assembled with metal ions/clusters and organic linkers. The fungibility of organic ligands and metal centers endow MOFs that are easy to design and synthesize. Based on their unique structure, multifarious MOFs with diverse functionalities have recently been widely applied in various research areas. Particularly striking is the application of photo-responsive MOFs in biological sensing and imaging. Notably, the photoelectronic properties make photo-responsive MOFs an ideal platform for cancer phototherapy. Moreover, ultrahigh porosities and tunable pore sizes allow MOFs to load anticancer drugs, further enhancing the antitumor efficiency. In this review, the categories and developing strategies of MOFs are briefly introduced. The application fields of MOFs in bioimaging, such as up-conversion fluorescence imaging, single/two-photon fluorescence bioimaging, magnetic resonance imaging, etc., are summarized. The working mechanism of MOFs in photo-responsive, photothermal therapy (PTT), and photodynamic therapy (PDT) are expounded. Examples of using MOFs for cancer treatment, including PTT, PDT, chemotherapy, and radiotherapy, are also demonstrated. Lastly, current limitations, challenges, and future perspectives for bioimaging and cancer treatment of MOFs are discussed. We believe that the versatile MOF will bring the dawn to the next generation of cancer treatment.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer.

Immune checkpoint blockade (ICB) therapy has evolved as a revolutionized therapeutic modality to eradicate tumor cells by releasing the brake of the antitumor immune response. However, only a subset of patients could benefit from ICB treatment currently. Phototherapy usually includes photothermal therapy (PTT) and photodynamic therapy (PDT). PTT exerts a local therapeutic effect by using photothermal agents to generate heat upon laser irradiation. PDT utilizes irradiated photosensitizers with a laser to produce reactive oxygen species to kill the target cells. Both PTT and PDT can induce immunogenic cell death in tumors to activate antigen-presenting cells and promote T cell infiltration. Therefore, combining ICB treatment with PTT/PDT can enhance the antitumor immune response and prevent tumor metastases and recurrence. In this review, we summarized the mechanism of phototherapy in cancer immunotherapy and discussed the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. Moreover, we also outlined the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB in preclinical and clinical studies. Finally, we analyzed the current challenges of this novel combination treatment regimen. We believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.

Quantification of prevalence, clinical characteristics, co-existence, and geographic variations of traditional Chinese medicine diagnostic patterns via latent tree analysis-based differentiation rules among functional dyspepsia patients.

BACKGROUND: Traditional Chinese Medicine (TCM) treatment strategies are guided by pattern differentiation, as documented in the eleventh edition of the International Classification of Diseases (ICD). However, no standards for pattern differentiation are proposed to ensure inter-rater agreement. Without standardisation, research on associations between TCM diagnostic patterns, clinical features, and geographical characteristics is also not feasible. This diagnostic cross-sectional study aimed to (i) establish the pattern differentiation rules of functional dyspepsia (FD) using latent tree analysis (LTA); (ii) compare the prevalence of diagnostic patterns in Hong Kong and Hunan; (iii) discover the co-existence of diagnostic patterns; and (iv) reveal the associations between diagnostic patterns and FD common comorbidities. METHODS: A total of 250 and 150 participants with FD consecutively sampled in Hong Kong and Hunan, respectively, completed a questionnaire on TCM clinical features. LTA was performed to reveal TCM diagnostic patterns of FD and derive relevant pattern differentiation rules. Multivariate regression analyses were performed to quantify correlations between different diagnostic patterns and between diagnostic patterns and clinical and geographical variables. RESULTS: At least one TCM diagnostic pattern was differentiated in 70.7%, 73.6%, and 64.0% of the participants in the overall (n = 400), Hong Kong (n = 250), and Hunan (n = 150) samples, respectively, using the eight pattern differentiation rules derived. 52.7% to 59.6% of the participants were diagnosed with two or more diagnostic patterns. Cold-heat complex (59.8%) and spleen-stomach dampness-heat (77.1%) were the most prevalent diagnostic patterns in Hong Kong and Hunan, respectively. Spleen-stomach deficiency cold was highly likely to co-exist with spleen-stomach qi deficiency (adjusted odds ratio (AOR): 53.23; 95% confidence interval (CI): 21.77 to 130.16). Participants with severe anxiety tended to have liver qi invading the stomach (AOR: 1.20; 95% CI: 1.08 to 1.33). CONCLUSIONS: Future updates of the ICD, textbooks, and guidelines should emphasise the importance of clinical and geographical variations in TCM diagnosis. Location-specific pattern differentiation rules should be derived from local data using LTA. In future, patients' pattern differentiation results, local prevalence of TCM diagnostic patterns, and corresponding TCM treatment choices should be accessible to practitioners on online clinical decision support systems to streamline service delivery.

Latent tree analysis for the identification and differentiation of evidence-based Traditional Chinese Medicine diagnostic patterns: A primer for clinicians.

BACKGROUND: A supplementary chapter on the diagnostic patterns of Traditional Medicine, including Traditional Chinese Medicine (TCM), was introduced into the latest edition of the International Classification of Diseases (ICD-11). However, evidence-based rules are yet to be developed for pattern differentiation in patients with specific conventional medicine diagnoses. Without such standardised rules, the level of diagnostic agreement amongst practitioners is unsatisfactory. This may reduce the reliability of practice and the generalisability of clinical research. PURPOSE: Using cross-sectional study data from patients with functional dyspepsia, we reviewed and illustrated a quantitative approach that combines TCM expertise and computer algorithmic capacity, namely latent tree analysis (LTA), to establish score-based pattern differentiation rules. REVIEW OF METHODS: LTA consists of six major steps: (i) the development of a TCM clinical feature questionnaire; (ii) statistical pattern discovery; (iii) statistical pattern interpretation; (iv) TCM diagnostic pattern identification; (v) TCM diagnostic pattern quantification; and (vi) TCM diagnostic pattern differentiation. Step (i) involves the development of a comprehensive questionnaire covering all essential TCM clinical features of the disease of interest via a systematic review. Step (ii) to (iv) required input from TCM experts, with the algorithmic capacity provided by Lantern, a dedicated software for TCM LTA. MOTIVATIONAL EXAMPLE TO ILLUSTRATE THE METHODS: LTA is used to quantify the diagnostic importance of various clinical features in each TCM diagnostic pattern in terms of mutual information and cumulative information coverage. LTA is also capable of deriving score-based differentiation rules for each TCM diagnostic pattern, with each clinical feature being provided with a numerical score for its presence. Subsequently, a summative threshold is generated to allow pattern differentiation. If the total score of a patient exceeded the threshold, the patient was diagnosed with that particular TCM diagnostic pattern. CONCLUSIONS: LTA is a quantitative approach to improving the inter-rater reliability of TCM diagnosis and addressing the current lack of objectivity in the ICD-11. Future research should focus on how diagnostic information should be coupled with effectiveness evidence derived from network meta-analysis. This will enable the development of an implementable diagnostics-to-treatment scheme for further evaluation. If successful, this scheme will transform TCM practice in an evidence-based manner, while preserving the validity of the model.

Fine particulate-bound arsenic and selenium from coal-fired power plants: Formation, removal and bioaccessibility.

The arsenic (As) and selenium (Se) in fine particulate matter (PM10) have attracted increasing attentions due to their health effects. However, the emission control of fine particulate-bound arsenic and selenium (fine particulate-bound As/Se) from coal-fired power plants still faces various challenges. Understanding the formation and characteristics of fine particulate-bound As/Se is crucial for developing specific control technologies. This study clarifies the formation mechanism, removal characteristics, and inhalation bioaccessibility of fine particulate-bound As/Se from industrial coal-fired power plants through methods including aerosol generation, As/Se speciation determination, and in vitro bioaccessibility testing. The findings demonstrated that PM1 from pulverized coal-fired (PC) boilers was enriched with As/Se in terms of concentration and mass distribution. Instead, As/Se was mainly distributed in PM2.5-10 from circulating fluidized bed (CFB) boilers. Limestone injection in CFB boilers promoted As/Se enrichment in coarse PM. Fine particulate-bound As was mainly formed by chemical adsorption of As vapors by Ca-minerals, while the formation of fine particulate-bound Se was closely related to active Ca-minerals and Fe-minerals. Furthermore, Ca-bound As was easy to remove by electrostatic precipitator (ESP) and the removal of physically adsorbed SeO2(s) was difficult, which was caused by the specific resistivity of different mineral components. Importantly, finer particulate-bound As/Se posed higher inhalation bioaccessibility, following the order of PM1 ≥ PM1-2.5 > PM2.5-10. In particular, Ca-bound Se in fine PM owned high bioaccessibility. Based on these findings, measures were proposed to suppress the formation of fine particulate-bound As/Se in the furnace and/or strengthen its removal in the post-combustion stage.

Research on a Silicon Gyroscope Interface Circuit Based on Closed-Loop Controlled Drive Loop.

The existing analysis methods for the silicon gyroscope drive loop, such as the perturbation method and period average method, cannot analyze the dynamic characteristics of the system. In this work, a linearized amplitude control model of the silicon gyroscope drive loop was established to analyze the stability and set-up time of the drive loop, and the vibration conditions of the silicon gyro were obtained. According to the above results, a new silicon gyroscope interface circuit was designed, using a 0.35 µm Bipolar-CMOS-DMOS (BCD) process, and the chip area was 4.5 mm × 4.0 mm. The application-specific integrated circuit (ASIC) of the silicon gyroscope was tested in combination with the sensitive structure with a zero stability of 1.14°/hr (Allen). The test results for the ASIC and the whole machine prove the correctness of the theoretical model, which reflects the effectiveness of the stability optimization of the closed-loop controlled drive loop of the silicon gyroscope circuit.

Four new polyprenylated acylphloroglucinol derivatives from Hypericum beanii.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (1-2), and two new biosynthetic precursors, hyperbeanins R-S (3-4), were isolated from Hypericum beanii, together with three known analogs (5-7). Compound 1 was one of type A PPAPs featured with unusual bicyclo[5.3.1]hendecane core. The structures of isolates were established by NMR spectroscopic methods, experimental electronic circular dichroism (ECD) spectra and comparisons with known compounds. Compounds 5 and 6 showed obvious hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage.

The characterization and candidate gene isolation for a novel male-sterile mutant ms40 in maize.

KEY MESSAGE: A novel genic male-sterile mutant ms40 was obtained from EMS treated RP125. The key candidate gene ZmbHLH51 located on chromosome 4 was identified by map-based cloning. This study further enriched the male sterile gene resources for both production applications and theoretical studies of abortion mechanisms. Maize male-sterile mutant 40 (ms40) was obtained from the progeny of the ethyl methanesulfonate (EMS) treated inbred line RP125. Genetic analysis indicated that the sterility was controlled by a single recessive nuclear gene. Cytological observation of anthers revealed that the cuticles of ms40 anthers were abnormal, and no Ubisch bodies were observed on the inner surface of ms40 anthers through scanning electron microscopy(SEM). Moreover, its tapetum exhibited delayed degradation and then blocked the formation of normal microspores. Using map-based cloning strategy, the ms40 locus was found to locate in a 282-kb interval on chromosome 4, and five annotated genes were predicted within this region. PCR-based sequencing detected a single non-synonymous SNP (G > A) that changed glycine (G) to arginine (A) in the seventh exon of Zm00001d053895, while no sequence difference between ms40 and RP125 was found for the other four genes. Zm00001d053895 encodes the bHLH transcription factor ZmbHLH51 which is localized in the nucleus. Phylogenetic analysis showed that ZmbHLH51 had the highest homology with Sb04g001650, a tapetum degeneration retardation (TDR) bHLH transcription factor in Sorghum bicolor. Co-expression analysis revealed a total of 1192 genes co-expressed with ZmbHLH51 in maize, 647 of which were anther-specific genes. qRT-PCR results suggested the expression levels of some known genes related to anther development were affected in ms40. In summary, these findings revealed the abortion characteristics of ms40 anthers and lay a foundation for further studies on the mechanisms of male fertility.