Band alignment of one-dimensional transition-metal dichalcogenide heterotubes.

One-dimensional (1D) van der Waals (vdW) heterotubes, where different kinds of 1D nanotubes coaxially nest inside each other, offer a flexible platform for promising applications. The various properties of these 1D heterotubes depend on their diameter. Here, we present a systematic theoretical investigation into the structural and electronic properties of two kinds of 1D transition-metal dichalcogenide (TMD) heterotubes. We demonstrate that the thermodynamic stability of 1D heterotubes is determined by their interlayer distance. Additionally, we establish that the band alignment transition changes from type I to type II in 1D TMD heterotubes. We identify two distinct transition mechanisms, originating from the exchange of either the valence band maximum or the conduction band minimum. According to an electrostatic model, the band alignment transition is attributed to the interlayer electric field effect, which depends on the heterotube diameter. The findings in this work provide valuable physical insights into the band alignment transition in 1D heterotubes and are instrumental for their potential applications in nanotechnology.

First-principles study of valley splitting of transition-metal dichalcogenides in MX2/CrI3 (M = W, Mo; X = S, Se, Te) van der Waals heterostructures.

The rapid development of valleytronics makes the application of two-dimensional (2D) transition-metal dichalcogenides (TMDs) in valley electronics important. As a new degree of freedom, valley splitting of TMDs has been achieved and tuned by many methods. Among them, using the magnetic proximity effect (MPE) generated from the interface of 2D van der Waals (vdW) heterostructures stacked with TMDs and one magnetic substrate, valley splitting can be achieved through band edge lifting at the adjacent K/K' valley. However, the comprehensive mechanism and strategy of valley splitting in 2D TMD heterostructures need to be explored ulteriorly. Here, we systematically investigated valley splitting of MX2 in MX2/CrI3 (M = W, Mo; X = S, Se, Te) vdW heterostructures using first-principles approaches. We demonstrated that twisting is an effective method to enhance valley splitting in MX2/CrI3 vdW heterostructures. Furthermore, we also showed a ∼10 times enhancement in valley splitting by changing the stacking patterns between WTe2 and CrI3 layers. We attribute this to the interlayer magnetic and electronic coupling between the two layers of the vdW heterostructure. The present results provide a theoretical basis and effective methods for tuning valley splitting 2D TMD heterostructures.

Metabolomic analysis in Amycolatopsis keratiniphila disrupted the competing ECO0501 pathway for enhancing the accumulation of vancomycin.

Vancomycin is a clinically important glycopeptide antibiotic against Gram-positive pathogenic bacteria, especially methicillin-resistant Staphylococcus aureus. In the mutant strain of Amycolatopsis keratiniphila HCCB10007 Δeco-cds4-27, the production of ECO-0501 was disrupted, but enhanced vancomycin yield by 55% was observed compared with the original strain of A. keratiniphila HCCB10007. To gain insights into the mechanism of the enhanced production of vancomycin in the mutant strain, comparative metabolomics analyses were performed between the mutant strain and the original strain, A. keratiniphila HCCB10007 via GC-TOF-MS and UPLC-HRMS. The results of PCA and OPLS-DA revealed a significant distinction of the intracellular metabolites between the two strains during the fermentation process. 64 intracellular metabolites, which involved in amino acids, fatty acids and central carbon metabolism, were identified as differential metabolites. The high-yield mutant strain maintained high levels of glucose-1-phosphate and glucose-6-phosphate and they declined with the increases of vancomycin production. Particularly, a strong association of fatty acids accumulation as well as 3,5-dihydroxyphenylacetic acid and non-proteinogenic amino acid 3,5-dihydroxyphenylglycine (Dpg) with enhancement of vancomycin production was observed in the high-yield mutant strain, indicating that the consumption of fatty acid pools might be beneficial for giving rise to 3,5-dihydroxyphenylacetic acid and Dpg which further lead to improve vancomycin production. In addition, the lower levels of glyoxylic acid and lactic acid and the higher levels of sulfur amino acids might be beneficial for improving vancomycin production. These findings proposed more advanced elucidation of metabolomic characteristics in the high-yield strain for vancomycin production and could provide potential strategies to enhance the vancomycin production.

Sulfenylation of ERK1/2: A novel mechanism for SO2-mediated inhibition of cardiac fibroblast proliferation.

Background: Endogenous sulfur dioxide (SO2) plays a crucial role in protecting heart from myocardial fibrosis by inhibiting the excessive growth of cardiac fibroblasts. This study aimed to investigate potential mechanisms by which SO2 suppressed myocardial fibrosis. Methods and results: Mouse model of angiotensin II (Ang II)-induced cardiac fibrosis and cell model of Ang II-stimulated cardiac fibroblast proliferation were employed. Our findings discovered that SO2 mitigated the aberrant phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) induced by Ang II, leading to a reduction of fibroblast proliferation. Mechanistically, for the first time, we found that SO2 sulfenylated ERK1/2, and inhibited ERK1/2 phosphorylation and cardiac fibroblast proliferation, while a sulfhydryl reducing agent dithiothreitol (DTT) reversed the above effects of SO2. Furthermore, mutant ERK1C183S (cysteine 183 to serine) abolished the sulfenylation of ERK by SO2, thereby preventing the inhibitory effects of SO2 on ERK1 phosphorylation and cardiac fibroblast proliferation. Conclusion: Our study suggested that SO2 inhibited cardiac fibroblast proliferation by sulfenylating ERK1/2 and subsequently suppressing ERK1/2 phosphorylation. These new findings might enhance the understanding of the mechanisms underlying myocardial fibrosis and emphasize the potential of SO2 as a novel therapeutic target for myocardial fibrosis.

Recent progress and outlooks in rhodamine-based fluorescent probes for detection and imaging of reactive oxygen, nitrogen, and sulfur species.

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.

The pharmacodynamic and mechanistic foundation for the antineoplastic effects of GFH009, a potent and highly selective CDK9 inhibitor for the treatment of hematologic malignancies.

To evade cell cycle controls, malignant cells rely upon rapid expression of select proteins to mitigate proapoptotic signals resulting from damage caused by both cancer treatments and unchecked over-proliferation. Cyclin-dependent kinase 9 (CDK9)-dependent signaling induces transcription of downstream oncogenes promoting tumor growth, especially in hyperproliferative 'oncogene-addicted' cancers, such as human hematological malignancies (HHMs). GFH009, a potent, highly selective CDK9 small molecule inhibitor, demonstrated antiproliferative activity in assorted HHM-derived cell lines, inducing apoptosis at IC50 values below 0.2 µM in 7/10 lines tested. GFH009 inhibited tumor growth at all doses compared to controls and induced apoptosis in a dose-dependent manner. Twice-weekly injections of GFH009 maleate at 10 mg/kg significantly prolonged the survival of MV-4-11 xenograft-bearing rodents, while their body weight remained stable. There was marked reduction of MCL-1 and c-MYC protein expression post-drug exposure both in vitro and in vivo. Through rapid 'on-off' CDK9 inhibition, GFH009 exerts a proapoptotic effect on HHM preclinical models triggered by dynamic deprivation of crucial cell survival signals. Our results mechanistically establish CDK9 as a targetable vulnerability in assorted HHMs and, along with the previously shown superior class kinome selectivity of GFH009 vs other CDK9 inhibitors, strongly support the rationale for currently ongoing clinical studies with this agent in acute myeloid leukemia and other HHMs.

[Melatonin-Mediated Inhibitory Effect on Hyperimmune Status of Acquired Aplastic Anemia].

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4+ and CD8+ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4+ and CD8+ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION: The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.

Rhodamine-based fluorescent sensors for the rapid and selective off-on detection of salicylic acid and their use in plant cell imaging.

Salicylic acid (SA) is a key hormone that regulates plant growth and immunity, and understanding the physiologic processes induced by SA enables the development of highly pathogen-resistant crops. Here, we report the synthesis of three new SA-sensors (R1-R3) from hydroxyphenol derivatives of a rhodamine-acylhydrazone scaffold and their characterization by NMR and HRMS. Spectroscopic analyses revealed that structural variations in R1-R3 resulted in sensors with different sensitivities for SA. Sensor R2 (with the 3-hydroxyphenyl modification) outperformed R1 (2-hydroxyphenyl) and R3 (4-hydroxyphenyl). The SA-detection limit of R2 is 0.9 µM with an ultra-fast response time (<60 s). In addition, their plant imaging indicated that designed sensor R2 is useful for the further study of SA biology and the discovery and development of new inducers of plant immunity.

[Deciphering Hypoplastic Myelodysplastic Syndrome and Aplastic Anemia via In-Depth Analysis of Lymphocyte Subsets].

OBJECTIVE: To explore the difference of lymphocyte subsets in peripheral blood (PB) between aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS) patients, meanwhile to compare the clinical parameters obtained from PB and bone marrow (BM). METHODS: The lymphocyte subsets in hypo-MDS (n=25) and AA (n=33) patients were investigated by flow cytometry. Meanwhile, the differences in PB cell counts, biochemical indicators, BM cell counts and abnormal chromosomes between the two groups were analyzed. RESULTS: The percentage of CD8+T cells in AA group was significantly higher than that in hypo-MDS group (P=0.001), while the percentage of CD4+ T cells and the CD4+/CD8+ ratio in AA group were obviously lower than those in hypo-MDS group (P=0.015 and 0.001, respectively). Furthermore, the proportion of CD4+ and CD8+ activated T (TA) cells, and memory Tregs in AA group was distinctly lower than those in hypo-MDS group (P=0.043, 0.015 and 0.024, respectively). Nevertheless, the percentage of CD8+ naive T (TN) cells in AA patients was remarkably higher (P=0.044). And hypo-MDS patients had declined lymphocyte counts (P=0.025), increased levels of total bilirubin (TBil), lactate dehydrogenase (LDH), vitamin B12 and proportion of BM blasts than AA patients (P=0.019, 0.023, 0.027 and 0.045, respectively). CONCLUSION: In this study it was confirmed that the percentages of CD4+ and CD8+ TA cells, memory Tregs and CD8+ TN cells were significantly different between AA and hypo-MDS patients, which provide an essential basis for the identification of these two diseases.

Prognostic value of sarcopenia in older adults with transcatheter aortic valve implantation: A systematic review and meta-analysis.

OBJECTIVE: We conducted this systematic review and meta-analysis to summarize the prevalence of sarcopenia and its impact on mortality in patients undergoing TAVI. METHOD: Medline, EMBASE, and PubMed were searched from inception to October 14, 2022 to retrieve eligible studies that assessed sarcopenia in patients undergoing TAVI. Pooled sarcopenia prevalence was calculated with 95% confidence interval (CI), and heterogeneity was estimated using the I2 test. Associations of sarcopenia with mortality of post-TAVI were expressed as hazard ratio (HR) or odds ratios (OR) and 95% CI. RESULTS: 13 studies involving 5248 patients (mean age from 78.1 to 84.9 years) undergoing TAVI were included. There were eleven studies defined sarcopenia based on loss of skeletal muscle mass index (SMI), while only two studies used low muscle mass plus low muscle strength and/or low physical performance. Overall, the pooled prevalence of sarcopenia in patients undergoing TAVI was 49% (95% CI 41%-58%). Sarcopenia was associated with an increased risk of long-term (≥1 year) mortality in patients after TAVI (HR 1.57, 95% CI 1.33-1.85, P < 0.001), with similar findings in the subgroups stratified by follow-up time, definition of sarcopenia, study location, and study design. Furthermore, the 1-, 2-, and 3-year cumulative probabilities of survival in patients with sarcopenia were significantly lower than non-sarcopenia (74.0% vs 91.0%, 68.3% vs 78.0%, and 72.6% vs 79.8%, all P < 0.05). CONCLUSIONS: Although there are substantial differences in diagnostic criteria, sarcopenia is highly prevalent in patients undergoing TAVI and its linked to increased long-term mortality after TAVI.

The effect of externally applied traditional Chinese medicine in diabetic foot: A systematic review and meta-analysis of 34 RCTs.

AIM: This study aimed to investigate the clinical efficacy of externally applied Traditional Chinese Medicine (TCM) on diabetic foot. METHODS: We searched the China Knowledge Network (CNKI), Wanfang Database, PubMed and Web of Science from inception to July 31, 2022, to find all randomized control trials (RCTs) related to externally applied TCMs in diabetic foot treatment. Information about the total effective rate, healing rate, and healing time were extracted. In addition, the relative risk (RR)/odds ratio (OR) or standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated. RESULTS: Finally, a total of 34 RCTs including 3758 patients were included in this meta-analysis. There were 5 articles that reported hydropathic compress with astrogalin, 14 articles that reported MEBO burn cream, 9 articles that reported compound cortex phellodendri liquid and 6 articles that reported Shengji Yuhong ointment. Compared with the basic treatment, the externally applied TCM (astrogalin, MEBO burn cream, compound cortex phellodendri liquid and Shengji Yuhong ointment) combined with basic treatment improved the total effective rate (RR = 1.31 [1.20, 1.42], P < 0.0001) and healing rate (RR = 1.84 [1.56, 2.17], P < 0.0001) and shortened the healing time (SMD = - 2.51 [- 3.39, - 1.63], P < 0.0001). CONCLUSION: Our systematic review and meta-analysis revealed that common TCM applied externally could significantly improve the clinical efficacy comparing to the basic treatment.

3.0 T unenhanced Dixon water-fat separation whole-heart coronary magnetic resonance angiography: compressed-sensing sensitivity encoding imaging versus conventional 2D sensitivity encoding imaging.

This study was aimed to investigate 3.0 T unenhanced Dixon water-fat whole-heart CMRA (coronary magnetic resonance angiography) using compressed-sensing sensitivity encoding (CS-SENSE) and conventional sensitivity encoding (SENSE) in vitro and in vivo. The key parameters of CS-SENSE and conventional 1D/2D SENSE were compared in vitro phantom study. In vivo study, fifty patients with suspected coronary artery disease (CAD) completed unenhanced Dixon water-fat whole-heart CMRA at 3.0 T using both CS-SENSE and conventional 2D SENSE methods. We compared mean acquisition time, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and the diagnostic accuracy between two techniques. In vitro study, CS-SENSE achieved better effectiveness between higher SNR/CNR and shorter scan times using the appropriate acceleration factor compared with conventional 2D SENSE. In vivo study, CS-SENSE CMRA had better performance than 2D SENSE in terms of the mean acquisition time, SNR and CNR (7.4 ± 3.2 min vs. 8.3 ± 3.4 min, P = 0.001; SNR: 115.5 ± 35.4 vs. 103.3 ± 32.2; CNR: 101.1 ± 33.2 vs. 90.6 ± 30.1, P < 0.001 for both). The diagnostic accuracy between CS-SENSE and 2D SENSE had no significant difference on a patient-based analysis (sensitivity: 97.3% vs. 91.9%; specificity: 76.9% vs. 61.5%; accuracy: 92.0% vs. 84.0%; P > 0.05 for each). Unenhanced CS-SENSE Dixon water-fat separation whole-heart CMRA at 3.0 T can improve the SNR and CNR, shorten the acquisition time while providing equally satisfactory image quality and diagnostic accuracy compared with 2D SENSE CMRA.

Prognostic value of temporal muscle thickness, a novel radiographic marker of sarcopenia, in patients with brain tumor: A systematic review and meta-analysis.

Sarcopenia has been identified as a prognostic factor among certain types of cancer. However, it is unclear whether there is prognostic value of temporalis muscle thickness (TMT), a potential surrogate for sarcopenia, in adults patients with brain tumors. Therefore, we searched the Medline, Embase, and PubMed to systematically review and meta-analyze the relationship between TMT and overall survival, progression-free survival, and complications in patients with brain tumors and the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) were evaluated. The quality in prognostic studies (QUIPS) instrument was employed to evaluate study quality. Nineteen studies involving 4570 patients with brain tumors were included for qualitative and quantitative analysis. Meta-analysis revealed thinner TMT was associated with poor overall survival (HR, 1.72; 95% CI, 1.45-2.04; P < 0.01) in patients with brain tumors. Sub-analyses showed that the association existed for both primary brain tumors (HR, 2.02; 95% CI, 1.55-2.63) and brain metastases (HR, 1.39; 95% CI, 1.30-1.49). Moreover, thinner TMT also was the independent predictor of progression-free survival in patients with primary brain tumors (HR, 2.88; 95% CI, 1.85-4.46; P < 0.01). Therefore, to improve clinical decision making it is important to integrate TMT assessment into routine clinical settings in patients with brain tumors.

Anti-thermal quenching phosphors based on the new phosphate host Ca3.6In3.6(PO4)6.

To enhance the working quality of WLEDs, considerable efforts have been made to upgrade the thermal quenching resistance of existing phosphors or design new anti-thermal quenching (ATQ) phosphors. Developing a new phosphate matrix material with special structural features has great importance for the fabrication of ATQ phosphors. By phase relationship and composition analysis, we have prepared a novel compound Ca3.6In3.6(PO4)6 (CIP). Coupling ab initio and Rietveld refinement techniques, the novel structure of CIP with partly vacant cationic positions was solved. Taking this unique compound as the host and using the inequivalent substitution of Dy3+ for Ca2+, a series of C1-xIP:Dy3+ rice-white emitting phosphors were successfully developed. When the temperature was raised to 423 K, the emission intensity of C1-xIP:xDy3+ (x = 0.01, 0.03, and 0.05) increased to 103.8%, 108.2%, and 104.5% of the original intensity at 298 K, respectively. Except for the strong bonding network and inherent cationic vacancy in the lattice, the ATQ property of the C1-xIP:Dy3+ phosphors is mainly attributed to the generation of interstitial oxygen from the substitution of unequal ions, which releases electrons with the thermal stimulus, causing anomalous emission. Finally, we have explored the quantum efficiency of C1-xIP:0.03Dy3+ phosphor and the working performance of PC-WLED prepared with C1-xIP:0.03Dy3+ phosphor and 365 nm chip. The research work sheds light on the relationship between lattice defects and thermal stability, and meanwhile offers a new strategy for the development of ATQ phosphors.

Electronic and magnetic properties of charged point defects in monolayer CrI3.

The two-dimensional magnetic material CrI3 has gained considerable attention owing to its promising applications in photoelectric and spin-related devices. Recently, various structural defects in CrI3 have been identified; however, the charge states of these defects have been mainly ignored. Here, we report on an investigation of the charged defects in monolayer CrI3, focused on the electronic and magnetic properties of the five most stable point defects using first-principles calculations. For positively charged I vacancies and negatively charged Cr vacancies, a blue- and red-shift of defect states near the Fermi level can be observed because of the atom relaxation. Our results also indicate that, among the five defects, the Cr interstitial defect has the smallest ionization energy of 0.34 eV, which makes its ionization easiest. Furthermore, a 0.2 µB enhancement of the magnetic moment on the nearest Cr atom can be found for the I vacancy and Cr interstitial defect. The investigation contributes to the atomic-scale comparison and understanding of the charged defects of monolayer CrI3.

Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors.

The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein. Computation modeling predicts that these compounds interact with the residues in the receptor binding domain. More importantly, these teicoplanin derivatives inhibit the entry of both pseudotyped SARS-CoV-2 Delta and Omicron variants. Our study demonstrates the feasibility of developing small molecule entry inhibitors by targeting the interaction of viral S protein and ACE2. Together, considering the proven safety and pharmacokinetics of teicoplanin as a glycopeptide antibiotic, the teicoplanin derivatives hold great promise of being repurposed as pan-SARS-CoV-2 inhibitors.

CRISPR/Cas9-mediated genome editing in vancomycin-producing strain Amycolatopsis keratiniphila.

Amycolatopsis is an important source of diverse valuable bioactive natural products. The CRISPR/Cas-mediated gene editing tool has been established in some Amycolatopsis species and has accomplished the deletion of single gene or two genes. The goal of this study was to develop a high-efficient CRISPR/Cas9-mediated genome editing system in vancomycin-producing strain A. keratiniphila HCCB10007 and enhance the production of vancomycin by deleting the large fragments of ECO-0501 BGC. By adopting the promoters of gapdhp and ermE*p which drove the expressions of scocas9 and sgRNA, respectively, the all-in-one editing plasmid by homology-directed repair (HDR) precisely deleted the single gene gtfD and inserted the gene eGFP with the efficiency of 100%. Furthermore, The CRISPR/Cas9-mediated editing system successfully deleted the large fragments of cds13-17 (7.7 kb), cds23 (12.7 kb) and cds22-23 (21.2 kb) in ECO-0501 biosynthetic gene cluster (BGC) with high efficiencies of 81%-97% by selecting the sgRNAs with a suitable PAM sequence. Finally, a larger fragment of cds4-27 (87.5 kb) in ECO-0501 BGC was deleted by a dual-sgRNA strategy. The deletion of the ECO-0501 BGCs revealed a noticeable improvement of vancomycin production, and the mutants, which were deleted the ECO-0501 BGCs of cds13-17, cds22-23 and cds4-27, all achieved a 30%-40% increase in vancomycin yield. Therefore, the successful construction of the CRISPR/Cas9-mediated genome editing system and its application in large fragment deletion in A. keratiniphila HCCB10007 might provide a powerful tool for other Amycolatopsis species.

Order of Onset of Physical Frailty and Cognitive Impairment and Risk of Repeated Falls in Community-Dwelling Older Adults.

OBJECTIVES: To examine whether physical frailty onset before, after, or in concert with cognitive impairment is differentially associated with fall incidence in community-dwelling older adults. DESIGN: A longitudinal observational study. SETTING AND PARTICIPANTS: Data from 1337 older adults age ≥65 years and free of physical frailty or cognitive impairment at baseline were obtained from the National Health Aging Trends Study (2011‒2017), a nationally representative cohort study of US older adult Medicare beneficiaries. METHODS: Participants were assessed annually for frailty (physical frailty phenotype) and cognitive impairment (bottom quintile of clock drawing test or immediate and delayed recall; or proxy-report of diagnosis of dementia or AD8 score of ≥2). Incident falls were ascertained annually via self-report. Multinomial logistic regression was performed to estimate the association between order of first onset of cognitive impairment and/or frailty and incident single or repeated falls in the 1-year interval following their first onset. RESULTS: Of the 1,337, 832 developed cognitive impairment first (termed "CI first"), 286 developed frailty first (termed "frailty first") and 219 had co-occurrence of cognitive impairment and frailty within one year (termed "CI-frailty co-occurrence") over 5 years. Overall, 491 (34.5%) had at least 1 fall during the 1-year interval following the onset of physical frailty and/or cognitive impairment. After adjustment, "CI-frailty co-occurrence" was associated with a more than 2-fold increased risk of repeated falls than "CI first" (odds ratio 2.35, 95% confidence interval 1.51‒3.67; P < .001). No significant difference was found between participants with "frailty first" and "CI first" (P = .07). In addition, the order of onset was not associated with risk of a single fall. CONCLUSIONS AND IMPLICATIONS: Older adults experiencing "CI-frailty co-occurrence" had the greatest risk of repeated falls compared with those with "CI first" and "frailty first". Fall risk screening should consider the order and timing of onset of physical frailty and cognitive impairment.

Interfacial effects on lithium-ion diffusion in two-dimensional lateral black phosphorus-graphene heterostructures.

Lateral heterostructures constructed from different two-dimensional (2D) materials can be potentially used in lithium-ion batteries (LIBs). The interface between two different components strongly affects LIB charge and discharge processes. Herein, the atomic structures, electronic properties, and Li-ion diffusion characteristics of lateral black phosphorus-graphene (BP-G) heterostructures are studied via first-principles calculations. The obtained results reveal that BP-G heterostructures with either zigzag (ZZ) or misoriented interfaces constructed according to Clar's rule possess a small number of interfacial states and are electronically stable. Furthermore, compared with the perfect ZZ interface of BP-G, Clar's interfaces provide a larger number of diffusion paths with much lower energy barriers. The findings of this study suggest that lateral BP-G heterostructures can provide insights for rapid charge and discharge processes in LIBs.

The microbiota regulates hematopoietic stem and progenitor cell development by mediating inflammatory signals in the niche.

The commensal microbiota regulates the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) in bone marrow. Whether and how the microbiota influences HSPC development during embryogenesis is unclear. Using gnotobiotic zebrafish, we show that the microbiota is necessary for HSPC development and differentiation. Individual bacterial strains differentially affect HSPC formation, independent of their effects on myeloid cells. Early-life dysbiosis in chd8-/- zebrafish impairs HSPC development. Wild-type microbiota promote HSPC development by controlling basal inflammatory cytokine expression in kidney niche, and chd8-/- commensals elicit elevated inflammatory cytokines that reduce HSPCs and enhance myeloid differentiation. We identify an Aeromonas veronii strain with immuno-modulatory activities that fails to induce HSPC development in wild-type fish but selectively inhibits kidney cytokine expression and rebalances HSPC development in chd8-/- zebrafish. Our studies highlight the important roles of a balanced microbiome during early HSPC development that ensure proper establishment of lineal precursor for adult hematopoietic system.