Construction and validation of a novel tumor morphology immune inflammatory nutritional score (TIIN score) for intrahepatic cholangiocarcinoma: a multicenter study.

BACKGROUND: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.

Development of a smartphone screening test for preclinical Alzheimer's disease and validation across the dementia continuum.

BACKGROUND: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10-20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. METHODS: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50-92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30-40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50-100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. DISCUSSION: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

Synthesis, physicochemical characterization, and investigation of anti-inflammatory activity of water-soluble PEGylated 1,2,4-Triazoles.

A series of water-soluble PEGylated 1,2,4-triazoles 5-8 were successfully synthesized from methyl 5-(chloromethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1. All of the water-soluble PEGylated 1,2,4-triazoles were characterized by FT-IR and 1H NMR spectroscopy. The solubility, in vitro plasma stability, and anti-inflammatory activity were also determined and compared to original methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates. For SAR study, all PEGylated 1,2,4-triazoles 5-8 performed potential anti-inflammatory activity on LPS-induced RAW 264.7 cells (IC50 = 3.42-7.81 µM). Moreover, the western blot result showed PEGylated 1,2,4-triazole 7d performed 5.43 and 2.37 folds inhibitory activity over iNOS and COX-2 expressions. On the other hand, the cell viability study revealed PEGylated 1,2,4-triazoles 7 and 8 with PEG molecular weight more than 600 presented better cell safety (cell viability > 95 %). Through the solubility and in vitro plasma stability studies, PEGylated 1,2,4-triazoles 7a-d exhibited higher hydrophilicity and prolonged 2.01 folds of half-life in compound 7d. Furthermore, the in vivo anti-inflammatory and gastric safety results indicated PEGylated 1,2,4-triazole 7d more effectively decreased the inflammatory response in edema and COX-2 expression and exhibited higher gastric safety than Indomethacin. Following the in vitro and in vivo study results, PEGylated 1,2,4-triazole 7d possessed favorable solubility, plasma stability features, safety, and significant anti-inflammatory activity to become the potential water-soluble anti-inflammatory candidate.

Synthesis, design, and antiproliferative evaluation of 6-(N-Substituted-methyl)pyrazolo[3,4-d]pyrimidines as the potent anti-leukemia agents.

Pyrazolopyrimidine derivatives, including pyrazolopyrimidines, 6-aminopyrazolopyrimidines, 6-[(formyloxy)methyl]pyrazolopyrimidines, 6-(hydroxymethyl)pyrazolopyrimidine, and 6-(aminomethyl)pyrazolopyrimidines have been successfully prepared and tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines. Among the tested pyrazolopyrimidine compounds, we found 6-aminopyrazolopyrimidines and 6-(aminomethyl)pyrazolopyrimidines with essential o-ClPh or p-ClPh substituted moieties on N-1 pyrazole ring exhibited the best IC50 inhibition activity for Jurkat cells. Furthermore, optimization of the SAR study on the C-6 position of pyrazolopyrimidine ring demonstrated that 6-(N-substituted-methyl)pyrazolopyrimidines 17b, 17d, and 19d possessed the significant IC50 inhibitory activity for the different leukemia cell lines, especially for Jurkat, K-562, and HL-60. On the other hand, further SAR inhibition and docking model studies revealed that compound 19d, which has a 3-(1H-imidazol-1-yl)propan-1-amino side-chain on the C-6 position, was able to form four hydrogen bonds with residues Ala226, Leu152, and Glu194 and specifically extended into the P1 pocket subsite with Aurora A, resulting in improved inhibitory activity almost similar to SNS-314. To explore the anti-cancer mechanism, compound 19d was measured by Western blot analysis in Jurkat T-cells, however, it showed non-responsibility to Aurora B. For the further structural modifications on the lateral chain of compound 19d, compounds 24 with longer lateral chain were designed and synthesized for testing leukemia cell lines. However, compounds 24 was significantly decrease inhibition potency against leukemia cell lines. Based on the in-vitro results, compounds 17b and 19d could be considered to be the best potential lead drug in our study for the development of new and effective therapies for leukemia treatment. On the other hand, the DHFR inhibition results indicated compound 19d possessed good inhibitory activity and better than the reported naphthalene derivative. Through further comparisons of the model superposition of three-dimensional (3D) conformations in DHFR, compound 19d presented a similar structural alignment to Methotrexate and the reported naphthalene derivative and led to similar drug-like functional relationships. As a results, compound 19d would be a potential DHFR inhibitor for anti-leukemia drug candidate.

Predictive value of HTS grade in patients with intrahepatic cholangiocarcinoma undergoing radical resection: a multicenter study from China.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model. METHODS: Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis. RESULTS: Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P < 0.05), and ROC results showed that HTS had the best predictive value. The Kaplan-Meier curve showed that the prognosis of ICC patients was worse with increasing HTS grade. Additionally, multivariate regression analysis showed that HTS grade, carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and vascular invasion were independent influencing factors for Overall survival (OS) and that HTS grade, CA19-9, CEA, vascular invasion and lymph node invasion were independent influencing factors for recurrence-free survival (RFS) (all P < 0.05). In the first, second, and third years of the training group, the AUCs for OS were 0.867, 0.902, and 0.881, and the AUCs for RFS were 0.849, 0.841, and 0.899, respectively. In the first, second, and third years of the validation group, the AUCs for OS were 0.727, 0.771, and 0.763, and the AUCs for RFS were 0.733, 0.746, and 0.801, respectively. Through the examination of calibration curves and using decision curve analysis (DCA), nomograms based on HTS grade showed excellent predictive performance. CONCLUSIONS: Our nomograms based on HTS grade had excellent predictive effects and may thus be able to help clinicians provide individualized clinical decision for ICC patients.

All-Optical Reconfigurable Excitonic Charge States in Monolayer MoS2.

Excitons are quasi-particles composed of electron-hole pairs through Coulomb interaction. Due to the atomic-thin thickness, they are tightly bound in monolayer transition metal dichalcogenides (TMDs) and dominate their optical properties. The capability to manipulate the excitonic behavior can significantly influence the photon emission or carrier transport performance of TMD-based devices. However, on-demand and region-selective manipulation of the excitonic states in a reversible manner remains challenging so far. Herein, harnessing the coordinated effect of femtosecond-laser-driven atomic defect generation, interfacial electron transfer, and surface molecular desorption/adsorption, we develop an all-optical approach to manipulate the charge states of excitons in monolayer molybdenum disulfide (MoS2). Through steering the laser beam, we demonstrate reconfigurable optical encoding of the excitonic charge states (between neutral and negative states) on a single MoS2 flake. Our technique can be extended to other TMDs materials, which will guide the design of all-optical and reconfigurable TMD-based optoelectronic and nanophotonic devices.

Quantum Emitters with Narrow Band and High Debye-Waller Factor in Aluminum Nitride Written by Femtosecond Laser.

Solid-state quantum emitters (QEs) are central components for photonic-based quantum information processing. Recently, bright QEs in III-nitride semiconductors, such as aluminum nitride (AlN), have attracted increasing interest because of the mature commercial application of the nitrides. However, the reported QEs in AlN suffer from broad phonon side bands (PSBs) and low Debye-Waller factors. Meanwhile, there is also a need for more reliable fabrication methods of AlN QEs for integrated quantum photonics. Here, we demonstrate that laser-induced QEs in AlN exhibit robust emission with a strong zero phonon line, narrow line width, and weak PSB. The creation yield of a single QE could be more than 50%. More importantly, they have a high Debye-Waller factor (>65%) at room temperature, which is the highest result among reported AlN QEs. Our results illustrate the potential of laser writing to create high-quality QEs for quantum technologies and provide further insight into laser writing defects in relevant materials.

Module-Level Polaritonic Thermophotovoltaic Emitters via Hierarchical Sequential Learning.

Thermophotovoltaic (TPV) generators provide continuous and high-efficiency power output by utilizing local thermal emitters to convert energy from various sources to thermal radiation matching the bandgaps of photovoltaic cells. Lack of effective guidelines for thermal emission control at high temperatures, poor thermal stability, and limited fabrication scalability are the three key challenges for the practical deployment of TPV devices. Here we develop a hierarchical sequential-learning optimization framework and experimentally realize a 6″ module-scale polaritonic thermal emitter with bandwidth-controlled thermal emission as well as excellent thermal stability at 1473 K. The 300 nm bandwidth thermal emission is realized by a complex photon polariton based on the superposition of Tamm plasmon polariton and surface plasmon polariton. We experimentally achieve a spectral efficiency of 65.6% (wavelength range of 0.4-8 µm) with statistical deviation less than 4% over the 6″ emitter, demonstrating industrial-level reliability for module-scale TPV applications.

Anti-SARS-CoV-2 Viral Activity of Sweet Potato Trypsin Inhibitor via Downregulation of TMPRSS2 Activity and ACE2 Expression In Vitro and In Vivo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Known as COVID-19, it has affected billions of people worldwide, claiming millions of lives and posing a continuing threat to humanity. This is considered one of the most extensive pandemics ever recorded in human history, causing significant losses to both life and economies globally. However, the available evidence is currently insufficient to establish the effectiveness and safety of antiviral drugs or vaccines. The entry of the virus into host cells involves binding to angiotensin-converting enzyme 2 (ACE2), a cell surface receptor, via its spike protein. Meanwhile, transmembrane protease serine 2 (TMPRSS2), a host surface protease, cleaves and activates the virus's S protein, thus promoting viral infection. Plant protease inhibitors play a crucial role in protecting plants against insects and/or microorganisms. The major storage proteins in sweet potato roots include sweet potato trypsin inhibitor (SWTI), which accounts for approximately 60% of the total water-soluble protein and has been found to possess a variety of health-promoting properties, including antioxidant, anti-inflammatory, ACE-inhibitory, and anticancer functions. Our study found that SWTI caused a significant reduction in the expression of the ACE2 and TMPRSS2 proteins, without any adverse effects on cells. Therefore, our findings suggest that the ACE2 and TMPRSS2 axis can be targeted via SWTI to potentially inhibit SARS-CoV-2 infection.

Evaluating the Therapeutic Effect of Hispidin on Prostate Cancer Cells.

Androgen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (PCa). However, prolonged ADT inevitably results in therapy resistance with the emergence of the castration-resistant PCa phenotype (CRPC). Hence, there is an urgent need to explore new treatment options capable of delaying PCa progression. Hispidin (HPD) is a natural polyketide primarily derived from plants and fungi. HPD has been shown to have a diverse pharmacological profile, exhibiting anti-inflammatory, antiviral, cardiovascular and neuro-protective activities. However, there is currently no research regarding its properties in the context of PCa treatment. This research article seeks to evaluate the anti-cancer effect of HPD and determine the underlying molecular basis in both androgen-sensitive PCa and CRPC cells. Cell growth, migration, and invasion assays were performed via the MTS method, a wound healing assay and the transwell method. To investigate if HPD affected the expression of proteins, Western blot analysis was conducted. Furthermore, apoptosis was assessed by Annexin V-FITC/PI staining and Western blot analyses. HPD exhibited a favorable pharmaceutical profile to inhibit cell growth; disrupt the cell cycle; attenuate wound healing, migration and invasion; and induce apoptosis in PCa cells in vitro. The mechanistic results demonstrated that HPD reduced AR, MMP-2 and MMP-9 expression and activated the caspase-related pathway, leading to programmed cell death in PCa cells. We showed the anti-cancer effect of HPD on PCa cells and confirmed its feasibility as a novel therapeutic agent. This study provides significant insights into the delineation of the molecular mechanism of HPD in PCa cells and the development of an effective and safe therapy using HPD to eliminate PCa progression.

A Systemic Approach to Isolate, Retrieve, and Characterize Trophoblasts from the Maternal Circulation Using a Centrifugal Microfluidic Disc and a Multiple Single-Cell Retrieval Strategy.

Rare cells in the blood often have rich clinical significance. Although their isolation is highly desirable, this goal remains elusive due to their rarity. This paper presents a systemic approach to isolate and characterize trophoblasts from the maternal circulation. A microfluidic rare cell disc assay (RaCDA) was designed to process an extremely large volume of up to 15 mL of blood in 30 min, depleting red blood cells (RBCs) and RBC-bound white blood cells (WBC) while isolating trophoblasts in the collection chip. To minimize cell loss, on-disc labeling of cells with fluorescent immuno-staining identified the trophoblasts. Retrieval of trophoblasts utilized an optimized strategy in which multiple single cells were retrieved within the same micropipette column, with each cell encapsulated in a fluid volume (50 nL) separated by an air pocket (10 nL). Further, whole-genome amplification (WGA) amplified contents from a few retrieved cells, followed by quality control (QC) on the success of WGA via housekeeping genes. For definitive confirmation of trophoblasts, short-tandem repeat (STR) of the WGA-amplified content was compared against STR from maternal WBC and amniocytes from amniocentesis. Results showed a mean recovery rate (capture efficiency) of 91.0% for spiked cells with a WBC depletion rate of 99.91%. The retrieval efficiency of single target cells of 100% was achieved for up to four single cells retrieved per micropipette column. Comparison of STR signatures revealed that the RaCDA can retrieve trophoblasts from the maternal circulation.

Classification guided thick fog removal network for drone imaging: ClassifyCycle.

The foggy images captured by drones are nonuniform due to inhomogeneous distribution of fog in higher altitude, leading to the obvious fog thickness differences in the images. This paper proposes a classification guided thick fog removal network for drone imaging, termed ClassifyCycle. The drone images are input into the proposed classification module (ICLFn) to enhance the reliability of follow-up learning network. The style migration module (ISMn) is introduced to reduce the image distortion, such as hue artifact and texture distort. The proposed network ClassifyCycle does not require paired foggy and corresponding fog-free datasets, avoiding the phenomena of overexposure, distortion, color deviation and fog residue after defogging. Extensive experimental results show that the proposed ClassifyCycle network surpasses the state-of-the-art algorithms on synthetic and realistic drone images captured in thick fog weather.

Exploring the EM-wave diffusion capabilities of axicon coding metasurfaces for stealth applications.

Coding metasurfaces for diffusion scattering of electromagnetic (EM) waves are important for stealth applications and have recently attracted researchers in physics and engineering communities. Typically, the available design approaches of coding metasurfaces lack a coding sequence design formula and sometimes cannot simultaneously ensure uniform diffusion and low reflected power intensity without extensive computational optimization. To the authors' best knowledge, the diffusion and radar-cross-section reduction (RCSR) of 2D axicon metasurfaces for cloaking and stealth applications have not been explored before. This article presents a single-layer coding metasurface design that exhibits an axicon phase mask on its aperture for efficient diffusion of EM-waves and RCSR of metallic objects. The proposed approach is robust and ensures greater than 10 dB of RCSR for normal incidence and a wide-range of off-normal incident angles. Theoretical calculations, numerical simulations, and experimental validations of the proposed axicon coding metasurface demonstrate that the 10 dB RCSR covers the frequency range of 15 to 35 GHz (fractional bandwidth is 80%) under normal incidence. Under off-normal incidence, the RCSR and the diffusive scattering behavior are preserved up to 60° regardless of the polarization of the far-field incident radar wave. Compared to other available approaches, the presented design approach is fast, robust, and can achieve more uniform diffusive scattering patterns with remarkable RCSR, which makes it very attractive for potential stealth applications.

Hybrid cubic-chessboard metasurfaces for wideband angle-independent diffusive scattering and enhanced stealth.

Because of the shortcomings associated with their scattering patterns, both the chessboard and cubic phased metasurfaces show non-perfect diffusion and hence sub-optimal radar cross section reduction (RCSR) properties. This paper presents a novel and powerful hybrid RCSR design approach for diffusive scattering by combining the unique attributes of cubic phase and chessboard phase profiles. The hybrid phase distribution is achieved by simultaneously imposing two distinct phase profiles (chessboard and cubic) on the hybrid metasurface area with the aid of geometric phase theory to further enhance the diffusive scattering and RCSR. It is shown in this paper that through the integration of cubic and chessboard phase profiles, a metasurface with the hybrid phase mask successfully overcomes all the above issues and shortcomings related to the RCSR of both chessboard and cubic metasurfaces. In addition, the proposed design leverages the unique scattering properties offered by these distinct phase profiles to achieve enhanced stealth capabilities over wide frequency ranges and for large incidence angles. Simulation and measurement results show that the designed hybrid metasurfaces using the proposed strategy achieved RCSR and low-level diffused scattering patterns from 12-28 GHz (80%) for normal incidence of a far-field CP radar plane wave. The hybrid metasurface shows a stable angular diffusion and RCSR performance when the azimuthal and elevation incidence angles are in the range of 0° → ± 75° which is wider than other designs in the literature. Therefore, this work can make objects significantly less detectable in complex radar environments when enhanced stealth is required.

Evidence for Quantum Stripe Ordering in a Triangular Optical Lattice.

Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.

Efficacy analysis and research progress of complementary and alternative medicines in the adjuvant treatment of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan.

H-type hypertension is a risk factor for chronic total coronary artery occlusion: a cross-sectional study from southwest China.

BACKGROUND: Chronic total coronary occlusion (CTO) is serious and the "last bastion" of percutaneous coronary intervention. Hypertension and hyperhomocysteinemia (HHCY) are synergistic and significantly increase cardiovascular event risk. The relationship between H-type hypertension and CTO remains unclear; thus, this cross-sectional study investigated this potential association. METHODS: Between January 2018 and June 2022, 1446 individuals from southwest China were recruited to participate in this study. CTO was defined as complete coronary artery occlusion persisting for over three months. H-type hypertension was defined as hypertension with plasma homocysteine levels ≥ 15 µmol/L. Multivariate logistic regression models were applied to assess the association between H-type hypertension and CTO. Receiver operating characteristic (ROC) curves were generated to determine the accuracy of H-type hypertension in predicting CTO. RESULTS: Of the 1446 individuals, 397 had CTO, and 545 had H-type hypertension. After multivariate adjustment, the odds ratio (OR) for CTO in individuals with H-type hypertension was 2.3-fold higher (95% CI 1.01-5.26) than that in healthy controls. The risk of CTO is higher in individuals with H-type hypertension than in those with isolated HHCY and hypertension. The area under the ROC curve for CTO was 0.685 (95% CI, 0.653-0.717) for H-type hypertension. CONCLUSIONS: In southwest China, H-type hypertension is significantly related to the occurrence of CTO. TRIAL REGISTRATION: This retrospective study was registered with the Chinese Clinical Trials Registry ( http://www.chictr.org.cn , ChiCTR2100050519.2.2).

Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases.

Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been approved so far. In this study, we show that Atranorin (C19H18O8), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells. Mechanistically, Atranorin inhibits NLRP3 activation induced cytokine secretion and cell pyroptosis through binding to ASC protein directly and therefore restraining ASC oligomerization. The pharmacological effect of Atranorin is evaluated in NLRP3 inflammasome-driven disease models. Atranorin lowers serum IL-1ß and IL-18 levels in LPS induced mice acute inflammation model. Also, Atranorin protects against MSU crystal induced mice gouty arthritis model and lowers ankle IL-1ß level. Moreover, Atranorin ameliorates intestinal inflammation and epithelial barrier dysfunction in DSS induced mice ulcerative colitis and inhibits NLRP3 inflammasome activation in colon. Altogether, our study identifies Atranorin as a novel NLRP3 inhibitor that targets ASC protein and highlights the potential therapeutic effects of Atranorin in NLRP3 inflammasome-driven diseases including acute inflammation, gouty arthritis and ulcerative colitis.

Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

BACKGROUND: Age-related declines in cognitive function may begin in midlife. PURPOSE: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment. METHODS: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors. RESULTS: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/µL) were associated with 5-year cognitive decline. CONCLUSIONS: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

Bacillus litorisediminis sp. nov., a Thermophilic Bacterium Isolated from Mangrove Sediment.

Two aerobic, Gram-staining-positive, rod-shaped, endospore-forming, thermophilic bacterial strains, designated FJAT-47801T and FJAT-47835, were isolated from the sediment collected from Zhangjiang Estuary Mangrove National Nature Reserve in Fujian Province, China. Growth was observed at 25-55 °C (optimum, 50 °C) and pH 7.0-9.0 (optimum, pH 7.0), with up to 4.0% (w/v) NaCl (optimum, without NaCl). Strains FJAT-47801T and FJAT-47835 showed the highest 16S rRNA gene sequence similarity to Bacillus oleivorans (98.5%). The 16S rRNA gene sequence similarity between FJAT-47801T and FJAT-47835 was 99.9% indicating they were the same species. Phylogenetic (based on 16S rRNA gene sequences) and phylogenomic (based on 120 conserved bacterial single-copy genes) trees showed that strains FJAT-47801T and FJAT-47835 should be affiliated to the genus Bacillus. The of menaquinone of strain FJAT-47801T was MK-7. The major fatty acids of strain FJAT-47801T were iso-C15:0, anteiso-C15:0, iso-C17:0, and C16:0. The major polar lipids strain FJAT-47801T were phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), and phosphatidylglycerol (PG). The genomic DNA G+C content of strain FJAT-47801T was 39.3%. The average nucleotide identity (84.3%) and the digital DNA-DNA hybridization value (28.1%) between strain FJAT-47801T and B. oleivorans CCTCC AB 2013353T were below the cut-off level for species delineation. Based on the above results, strain FJAT-47801T represents a novel species of the genus Bacillus, for which the name Bacillus litorisediminis sp. nov., is proposed. The type strain is FJAT-47801T (=GDMCC 1.2712T = JCM 34875T).