Persistent Chirality-Induced Spin-Selectivity Effect in Circular Helix Molecules.

The spin-orbit coupling (SOC), the dynamics of the nonequilibrium transport process, and the breaking of time-reversal and space-inversion symmetries have been regarded as key factors for the emergence of chirality-induced spin selectivity (CISS) and chirality-dependent spin currents in helix molecules. In this work, we demonstrated the generation of persistent CISS currents in various circular single-stranded DNAs and 310-helix proteins for the first time, regardless of whether an external magnetic flux is applied or not. This new CISS effect presents only in equilibrium transport processes, distinct from the traditional CISS observed in nonequilibrium transport processes and linear helix molecules; we term it as the PCISS effect. Notably, PCISS manifests irrespective of whether the SOC is chirality-driven or stems from heavy-metal substrates, making it an efficient way to generate chirality-locked pure spin currents. Our research establishes a novel paradigm for examining the underlying physics of the CISS effect.

Ling-Gui-Zhu-Gan decoction ameliorates nonalcoholic fatty liver disease via modulating the gut microbiota.

Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis. Metagenomics, metabolomics, and transcriptomics were used to explore the structure and metabolism of the gut microbiota. LG significantly improved hepatic function and decreased lipid droplet accumulation in HD-induced NAFLD mice. LG reversed the structure of the gut microbiota that is damaged by HD and improved intestinal barrier function. Meanwhile, the LG group showed a lower total blood bile acids (BAs) concentration, a shifted BAs composition, and a higher fecal short-chain fatty acids (SCFAs) concentration. Furthermore, LG could regulate the hepatic expression of genes associated with the primary BAs biosynthesis pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study suggested that LG could ameliorate NAFLD by altering the structure and metabolism of gut microbiota, while BAs and SCFAs are considered possible mediating substances. IMPORTANCE: Until now, there has still been no study on the gut microbiota and metabolomics of Ling-Gui-Zhu-Gan decoction (LG) in nonalcoholic fatty liver disease (NAFLD) mouse models. Our study is the first to report on the reshaping of the structure and metabolism of the gut microbiota by LG, as well as explore the potential mechanism underlying the improvement of NAFLD. Specifically, our study demonstrates the potential of gut microbial-derived short-chain fatty acids (SCFAs) and blood bile acids (BAs) as mediators of LG therapy for NAFLD in animal models. Based on the results of transcriptomics, we further verified that LG attenuates NAFLD by restoring the metabolic disorder of BAs via the up-regulation of Fgf15/FXR in the ileum and down-regulation of CYP7A1/FXR in the liver. LG also reduces lipogenesis in NAFLD mice by mediating the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which then contributes to reducing hepatic inflammation and improving intestinal barrier function to treat NAFLD.

[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

Serum cytokines profile changes in amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015). Conclusion: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS.

The Impact of Different Regions of Interest on Shear Wave Elastography Assessment of the Meniscus in the Knee Joint.

RATIONALE AND OBJECTIVES: To investigate the impact of different regions of interest (ROI) on the assessment of shear wave elastography (SWE) in evaluating the meniscus of the knee joint. MATERIALS AND METHODS: After ethical approval, a total of 141 participants were enrolled in this prospective study from February to October 2023. SWE was utilized to evaluate the anterior horn of the lateral meniscus (LM) and medial meniscus (MM), using two different ROIs (ROI-Small and ROI-Trace) to measure the elastic mean value (Emean) and elastic maximum value (Emax). The differences in elasticity values between the normal menisci and torn menisci were compared, and the impact of different ROI selection methods on the diagnostic performance of elastic parameters in the torn menisci was assessed using receiver operating characteristic (ROC) curves. RESULTS: In Emean comparison, only MM in the tear group showed higher ROI-S than ROI-T. When comparing Emax, all ROI-T values were higher than the ROI-S values, and this difference was statistically significant. Different sizes of ROI did not significantly impact the diagnostic performance of Emean in LM and MM, nor the diagnostic effectiveness of Emax in LM. However, only the area under the curve (AUC) of MM for Emax in both ROI-S and ROI-T showed a statistically significant difference. CONCLUSION: The shear wave elasticity values and diagnostic performance may vary depending on the ROI settings. Therefore, it is recommended to use a 2 mm diameter ROI placed at the central position of the meniscus, with Emean as the elasticity index.

Metabolic adaptations of Microbacterium sediminis YLB-01 in deep-sea high-pressure environments.

The deep-sea environment is an extremely difficult habitat for microorganisms to survive in due to its intense hydrostatic pressure. However, the mechanisms by which these organisms adapt to such extreme conditions remain poorly understood. In this study, we investigated the metabolic adaptations of Microbacterium sediminis YLB-01, a cold and stress-tolerant microorganism isolated from deep-sea sediments, in response to high-pressure conditions. YLB-01 cells were cultured at normal atmospheric pressure and 28 ℃ until they reached the stationary growth phase. Subsequently, the cells were exposed to either normal pressure or high pressure (30 MPa) at 4 ℃ for 7 days. Using NMR-based metabolomic and proteomic analyses of YLB-01 cells exposed to high-pressure conditions, we observed significant metabolic changes in several metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. In particular, the high-pressure treatment stimulates cell division and triggers the accumulation of UDP-glucose, a critical factor in cell wall formation. This finding highlights the adaptive strategies used by YLB-01 cells to survive in the challenging high-pressure environments of the deep sea. Specifically, we discovered that YLB-01 cells regulate amino acid metabolism, promote carbohydrate metabolism, enhance cell wall synthesis, and improve cell membrane fluidity in response to high pressure. These adaptive mechanisms play essential roles in supporting the survival and growth of YLB-01 in high-pressure conditions. Our study offers valuable insights into the molecular mechanisms underlying the metabolic adaptation of deep-sea microorganisms to high-pressure environments. KEY POINTS: • NMR-based metabolomic and proteomic analyses were conducted on Microbacterium sediminis YLB-01 to investigate the significant alterations in several metabolic pathways in response to high-pressure treatment. • YLB-01 cells used adaptive strategies (such as regulated amino acid metabolism, promoted carbohydrate metabolism, enhanced cell wall synthesis, and improved cell membrane fluidity) to survive in the challenging high-pressure environment of the deep sea. • High-pressure treatment stimulated cell division and triggered the accumulation of UDP-glucose, a critical factor in cell wall formation, in Microbacterium sediminis YLB-01 cells.

Eomesodermin expression in CD4+T-cells associated with disease progression in amyotrophic lateral sclerosis.

AIM: To clarify the role of Eomesodermin (EOMES) to serve as a disease-relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4+T subsets in amyotrophic lateral sclerosis (ALS). METHODS: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T-cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1-year longitudinal follow-ups, the ALSFRS-R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort. RESULTS: In the derivation cohort, the CD4+EOMES+T-cell subsets were significantly increased (p < 0.001). EOMES+ subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4+EOMES+T-cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p = .010) and worse prognosis (p = .003). CONCLUSIONS: We demonstrated that increased CD4+EOMES+T-cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS.

The device performance limit of in-plane monolayer VTe2/WTe2 heterojunction-based field-effect transistors.

To overcome the scaling restriction on silicon-based field-effect transistors (FETs), two-dimensional (2D) transition metal dichalcogenides (TMDs) have been strongly proposed as alternative materials. To explore the device performance limit of TMD-based FETs, in this work, the ab initio quantum transport approach is utilized to study the transport properties of monolayer VTe2/WTe2 heterojunction-based FETs possessing double gates (DGs) with a 5 nm gate length (Lg). Our theoretical simulations demonstrate that the DG-cold-source VTe2/WTe2 FETs with a 5 nm Lg and 2 or 3 nm proper underlap (UL) meet the basic requirements of the on-state current (Ion), power dissipation (PDP), and delay time (τ) for the 2028 needs of the International Technology Roadmap for Semiconductor (ITRS) 2013, which ensures their high-performance and low-power-dissipation device applications. Moreover, the DG-cold-source VTe2/WTe2-based FETs with a 3 nm Lg and 2 or 3 nm UL meet the high-performance requirements of Ion, τ, and PDP for the 2028 needs of ITRS 2013. Additionally, by further considering the negative capacitance technology in devices, the parameters τ, Ion, and PDP of the VTe2/WTe2-based FETs with a 1 nm Lg and 3 nm UL meet well with the 2028 needs for ITRS 2013 towards high-performance device applications. Our theoretical results uncover that the 2D DG-cold-source VTe2/WTe2 FETs can be used as a new kind of promising material candidate to drive the scaling of Moore's law down to 1 nm.

Spin-Dependent Destructive and Constructive Quantum Interference Associated with Chirality-Induced Spin Selectivity in Single Circular Helix Molecules.

Chirality-induced spin selectivity (CISS) effect in straight helical molecules has received intense studies in past decade; however, the CISS effect in circular helical molecules (CHMs) has still rarely been explored. Here, we have constructed single CHMs having chirality-induced spin-orbit coupling (SOC) and connected by two nonmagnetic leads and successfully gained the required conditions for CISS effect occurring in CHMs for the first time. Our results uncover that only when the CHMs form a closed loop and when the lattice positions are coupled asymmetrically with both leads does the CISS effect occur. More importantly, the CISS-associated spin-dependent destructive and constructive quantum interference (QI) together with their phase transition appears in CHMs. The combination of CISS effect and spin-dependent QI phenomena opens up a new door to understand the underlying physics of the CISS effect in helical molecules.

[Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method].

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

New halimane and clerodane diterpenoids from Croton cnidophyllus.

Three new halimane furanoditerpenoids (1-3) and three new clerodane furanoditerpenoids (4-6), along with seven known terpenoids including four pimarane diterpenoids (7-10) and three norisoprenoids (11-13) were isolated from the 95% EtOH extracts of the plants of Croton cnidophyllus. The 2D structures including absolute configuration of new furanoditerpenoids (1-6) were elucidated by analysis of their HRMS and NMR data as well as comparison of experimental and calculated ECD curves. Bioassay revealed that two compounds (8 and 9) possessed certain inhibitory effects against NO production stimulated by LPS, with IC50 values of 19.00 ± 1.76 and 21.61 ± 1.11 µM, respectively.

Multi-Fold Fan-Shape Surface State Induced by an Isolated Weyl Phonon Beyond No-Go Theorem.

Absence of any surface arc state has been regarded as the fundamental property of singular Weyl points, because they are circumvented from the Nielsen-Ninomiya no-go theorem. In this work, through systematic investigations on topological properties of isolated Weyl phonons (IWPs) surrounded by closed Weyl nodal walls (WNWs), which are located at the Brillouin zone (BZ) boundaries of bosonic systems, it uncovers that a new kind of phononic surface state, that is, the multi-fold fan-shape surface state named by us, is exhibited to connect the projections of IWP and WNWs. Importantly, the number of fan leaves in this surface state is associated with the Chern number of IWP. Moreover, the topological features of charge-two IWP in K2 Mg2 O3 (SG No. 96) and charge-four IWP in Nb3 Al2 N (SG No. 213) confirm further the above fundamental properties of this kind of surface state. The theoretical work not only provides an effective way to seek for IWPs as well as to determine their Chern number in real materials, but also uncovers a new class of surface states in the topological Weyl complex composed of IWPs and WNWs.

[Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema].

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.

Quintuple Function Integration in Two-Dimensional Cr(II) Five-Membered Heterocyclic Metal Organic Frameworks via Tuning Ligand Spin and Lattice Symmetry.

Two-dimensional (2D) semiconductors (SCs) integrated with two or more functions are the cornerstone for constructing multifunctional nanodevices but remain largely limited. Here, by tuning the spin state of organic linkers and the symmetry/topology of crystal lattices, we predict a class of unprecedented multifunctional SCs in 2D Cr(II) five-membered heterocyclic metal organic frameworks that simultaneously possess auxetic effect, room-temperature ferrimagnetism, chiral ferroelectricity (FE), electrically reversible spin polarization, and topological nodal lines/points. Taking 2D Cr(TDZ)2 (TDZ = 1.2.5-thiadiazole) as an exemplification, the auxetic effect is produced by the antitetra-chiral lattice structure. The high temperature ferrimagnetism originates from the strong d-p direct magnetic exchange interaction between Cr cations and TDZ doublet radical anions. Meanwhile, the clockwise-counterclockwise alignment of TDZ's dipoles results in unique 2D chiral FE with atomic-scale vortex-antivortex states. 2D Cr(TDZ)2 is an intrinsic bipolar magnetic SC where half-metallic conduction with switchable spin-polarization direction can be induced by applying a gate voltage. In addition, the symmetry of the little group C4 of the lattice structure endows 2D Cr(TDZ)2 with topological nodal lines and a quadratic nodal point in the Brillouin zone near the Fermi level.

Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients.

BMF-AS1/BMF Promotes Diabetic Vascular Calcification and Aging both In Vitro and In Vivo.

Vascular calcification and aging often increase morbidity and mortality in patients with diabetes mellitus (DM); however, the underlying mechanisms are still unknown. In the present study, we found that Bcl-2 modifying factor (BMF) and BMF antisense RNA 1 (BMF-AS1) were significantly increased in high glucose-induced calcified and senescent vascular smooth muscle cells (VSMCs) as well as artery tissues from diabetic mice. Inhibition of BMF-AS1 and BMF reduced the calcification and senescence of VSMCs, whereas overexpression of BMF-AS1 and BMF generates the opposite results. Mechanistic analysis showed that BMF-AS1 interacted with BMF directly and up-regulated BMF at both mRNA and protein levels, but BMF did not affect the expression of BMF-AS1. Moreover, knocking down BMF-AS1 and BMF suppressed the calcification and senescence of VSMCs, and BMF knockout (BMF-/-) diabetic mice presented less vascular calcification and aging compared with wild type diabetic mice. In addition, higher coronary artery calcification scores (CACs) and increased plasma BMF concentration were found in patients with DM, and there was a positive correlation between CACs and plasma BMF concentration. Thus, BMF-AS1/BMF plays a key role in promoting high glucose-induced vascular calcification and aging both in vitro and in vivo. BMF-AS1 and BMF represent potential therapeutic targets in diabetic vascular calcification and aging.

Evaluation of an automated CRISPR-based diagnostic tool for rapid detection of COVID-19.

The performance of an automated commercial CRISPR/Cas based technology was evaluated and compared with routine RT-PCR testing to diagnose COVID-19. Suspected and discharged COVID-19 cases were included and tested with CRISPR-based SARS-CoV-2 test and RT-PCR assay using throat swab and sputum specimens. The diagnostic yield was calculated and compared using the McNemar test. A total of 437 patients were included for analysis, including COVID-19 (n = 171), discharged cases (n = 155), and others (n = 111). For the diagnosis of COVID-19, the CRISPR-SARS-CoV-2 test had a sensitivity and specificity of 98.2% (168/171) and 100.0% (266/266), respectively; the RT-PCR test had a sensitivity and specificity of 100.0% (171/171) and 100.0% (266/266), respectively. No significant difference was found in the sensitivity of CRISPR-SARS-CoV-2 and RT-PCR. In conclusion, the CRISPR-SARS-CoV-2 test had a comparable performance with RT-PCR and showed several advantages, such as short assay time, low cost, and no requirement for expensive equipment.

Tetrahydrocurcumin regulates the tumor immune microenvironment to inhibit breast cancer proliferation and metastasis via the CYP1A1/NF-κB signaling pathway.

The NF-κB signaling pathway is overactivated in tumor cells, and the activation of the NF-κB signaling pathway releases a large number of inflammatory factors, which enhance tumor immunosuppression and promote tumor metastasis. The cytochrome P450 (CYP450) system consists of important metabolic enzymes present in different tissues and progressive tumors, which may lead to changes in the pharmacological action of drugs in inflammatory diseases such as tumors. In this study, the anticancer effect of tetrahydrocurcumin (THC), an active metabolite of curcumin, on breast cancer cells and the underlying mechanism were investigated. Result showed that THC selectively inhibited proliferation and triggered apoptosis in breast cancer cells in a concentration- and time-dependent manner. Moreover, THC-induced cell apoptosis via a mitochondria-mediated pathway, as indicated by the upregulated ratio of Bax/Bcl-2 and reactive oxygen species (ROS) induction. In addition, THC could affect the CYP450 enzyme metabolic pathway and inhibit the expression of CYP1A1 and activation of the NF-κB pathway, thereby inhibiting the migration and invasion of breast cancer cells. Furthermore, after overexpression of CYP1A1, the inhibitory effects of THC on the proliferation, metastasis, and induction of apoptosis in breast cancer cells were weakened. The knockdown of CYP1A1 significantly enhanced the inhibitory effect of THC on the proliferation, metastasis, and apoptosis induction of breast cancer cells. Notably, THC exhibited a significant tumor growth inhibition and anti-pulmonary metastasis effect in a tumor mouse model of MCF-7 and 4T1 cells by regulating the tumor immunosuppressive microenvironment. Collectively, these results showed that TH could effectively trigger apoptosis and inhibit the migration of breast cancer cells via the CYP1A1/NF-κB signaling pathway, indicating that THC serves as a potential candidate drug for the treatment of breast cancer.

Chiral Iron Porphyrins Catalyze Enantioselective Intramolecular C(sp3 )-H Bond Amination Upon Visible-Light Irradiation.

Iron-catalyzed asymmetric amination of C(sp3 )-H bonds is appealing for synthetic applications due to the biocompatibility and high earth abundance of iron, but examples of such reactions are sparse. Herein we describe chiral iron complexes of meso- and ß-substituted-porphyrins that can catalyze asymmetric intramolecular C(sp3 )-H amination of aryl and arylsulfonyl azides to afford chiral indolines (29 examples) and benzofused cyclic sulfonamides (17 examples), respectively, with up to 93 % ee (yield: up to 99 %) using 410 nm light under mild conditions. Mechanistic studies, including DFT calculations, for the reactions of arylsulfonyl azides reveal that the Fe(NSO2 Ar) intermediate generated in situ under photochemical conditions reacts with the C(sp3 )-H bond through a stepwise hydrogen atom transfer/radical rebound mechanism, with enantioselectivity arising from cooperative noncovalent interactions between the Fe(NSO2 Ar) unit and the peripheral substituents of the chiral porphyrin scaffold.

Compromised item detection: A Bayesian change-point perspective.

Psychometric methods for accurate and timely detection of item compromise have been a long-standing topic. While Bayesian methods can incorporate prior knowledge or expert inputs as additional information for item compromise detection, they have not been employed in item compromise detection itself. The current study proposes a two-phase Bayesian change-point framework for both stationary and real-time detection of changes in each item's compromise status. In Phase I, a stationary Bayesian change-point model for compromise detection is fitted to the observed responses over a specified time-frame. The model produces parameter estimates for the change-point of each item from uncompromised to compromised, as well as structural parameters accounting for the post-change response distribution. Using the post-change model identified in Phase I, the Shiryaev procedure for sequential testing is employed in Phase II for real-time monitoring of item compromise. The proposed methods are evaluated in terms of parameter recovery, detection accuracy, and detection efficiency under various simulation conditions and in a real data example. The proposed method also showed superior detection accuracy and efficiency compared to the cumulative sum procedure.