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Abstract Hexagonal boron nitride (hBN) has recently been demonstrated to contain optically polarized and detected electron spins that can be utilized for implementing qubits and quantum sensors in nanolayered-devices. Understanding the coherent dynamics of microwave driven spins in hBN is of crucial importance for advancing these emerging new technologies. Here, we demonstrate and study the Rabi oscillation and related phenomena of a negatively charged boron vacancy (V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − ) spin ensemble in hBN. We report on different dynamics of the V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − spins at weak and strong magnetic fields. In the former case the defect behaves like a single electron spin system, while in the latter case it behaves like a multi-spin system exhibiting multiple-frequency dynamical oscillation as beat in the Ramsey fringes. We also carry out theoretical simulations for the spin dynamics of V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − and reveal that the nuclear spins can be driven via the strong electron nuclear coupling existing in V $${}_{{{{{{{{\rm{B}}}}}}}}}^{-}$$ B − center, which can be modulated by the magnetic field and microwave field.

Abstract Background The drug resistance of tumor stem cells is an obstacle in gastric cancer (GC) treatment and the high expression of ABC transporters is a classic reason for drug resistance. This study aimed to construct a reliable GC drug-resistant stem cell model and explore the inhibitory effect and mechanism of Yi-qi-hua-yu-jie-du medicated serum (YQHY) on the drug resistance of GC stem cells based on ABC transporters. Methods The tumor stemness biomarker CD44 was primary identification from WGCNA. The magnetic-activated cell sorting (MACS) method was used to separate CD44( +)BGC823/5-Fu (BGC823/5–Fu-CSCs) cells and the stemness characteristics were verified from multiple dimensions. Then, the drug resistance index and expression of ABC transporter genes MDR1 and MRP1 were detected in CD44(−)/CD44(+) cells. The inhibition and apoptosis rates of the cells administrated with YQHY or/and 5-Fu were calculated to confirm that YQHY can suppress the drug resistance of BGC823/5-Fu-CSCs. Afterwards, the effects of YQHY on the expression of MDR1 and MRP1 and the activation of the PI3K/Akt/Nrf2 pathway were observed. Finally, under the administration of IGF-1 (the activator of PI3K/Akt pathway) and Nrf2 siRNA, the mechanism of YQHY on reversing the drug resistance of BGC823/5–Fu-CSCs through inhibiting the expression of MDR1 and MRP1 via PI3K/Akt/Nrf2 was verified. Results CD44 was a reliable GC stemness biomarker and can be applied to construct the drug-resistant GC stem cell model CD44(+)BGC823/5-Fu. The growth rate, cell proliferation index, soft agar colony formation, expression of stemness specific genes and tumorigenesis ability of CD44(+)BGC823/5-Fu cells were significantly higher than those of CD44(−)BGC823/5-Fu cells. BGC823/5–Fu-CSCs exhibited strong drug resistance to 5-Fu and high expression of ABC transporter genes MDR1 and MRP1 compared to CD44(-) cells. YQHY increased the inhibition and apoptosis rates to efficiently inhibit the drug resistance of BGC823/5–Fu-CSCs. Meanwhile, it suppressed the expression of MDR1 and MRP1 and restrained the activation of PI3K/Akt/Nrf2 signaling pathway. Finally, it was found that IGF-1 partially restored the activation of PI3K/Akt/Nrf2 pathway, alleviated the inhibition of MDR1 and MRP1, blocked the proliferation-inhibitory and apoptosis-promotion effects. YQHY and si-Nrf2 synergistically suppressed the MDR1/MRP1 expression and the drug resistance of BGC823/5–Fu-CSCs. Conclusions CD44 was a reliable GC stemness biomarker, and the high expression of ABC transporter genes MDR1 and MRP1 was an important feature of drug-resistant stem cells. YQHY inhibited the MDR1 and MRP1 expression via PI3K/Akt/Nrf2 pathway, thus reversing the drug resistance of BGC823/5–Fu-CSCs.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease where substantial heterogeneity in clinical presentation urgently requires a better stratification of patients for the development of drug trials and clinical care. In this study we explored stratification through a crowdsourcing approach, the DREAM Prize4Life ALS Stratification Challenge. Using data from >10,000 patients from ALS clinical trials and 1479 patients from community-based patient registers, more than 30 teams developed new approaches for machine learning and clustering, outperforming the best current predictions of disease outcome. We propose a new method to integrate and analyze patient clusters across methods, showing a clear pattern of consistent and clinically relevant sub-groups of patients that also enabled the reliable classification of new patients. Our analyses reveal novel insights in ALS and describe for the first time the potential of a crowdsourcing to uncover hidden patient sub-populations, and to accelerate disease understanding and therapeutic development.

A new species of Oreocharis, O. guangwushanensis from the Sichuan Province of south-western China, is described and illustrated here. This new species has a pink corolla that is different from other species of Oreocharis in southwest China and, although it is morphologically similar to O. ronganensis and O. reticuliflora, it has significant differences in the colour and shape of the corolla, the apex of the corolla limb, shape and indumentum of the filaments and a shorter pistil. A detailed description, colour photographs, distribution and habitat, as well as the IUCN conservation status, are also provided.

Abstract Bismuth-based materials (e.g., metallic, oxides and subcarbonate) are emerged as promising electrocatalysts for converting CO2 to formate. However, Bio-based electrocatalysts possess high overpotentials, while bismuth oxides and subcarbonate encounter stability issues. This work is designated to exemplify that the operando synthesis can be an effective means to enhance the stability of electrocatalysts under operando CO2RR conditions. A synthetic approach is developed to electrochemically convert BiOCl into Cl-containing subcarbonate (Bi2O2(CO3) x Cl y ) under operando CO2RR conditions. The systematic operando spectroscopic studies depict that BiOCl is converted to Bi2O2(CO3) x Cl y via a cathodic potential-promoted anion-exchange process. The operando synthesized Bi2O2(CO3) x Cl y can tolerate − 1.0 V versus RHE, while for the wet-chemistry synthesized pure Bi2O2CO3, the formation of metallic Bio occurs at − 0.6 V versus RHE. At − 0.8 V versus RHE, Bi2O2(CO3) x Cl y can readily attain a FEHCOO- of 97.9%, much higher than that of the pure Bi2O2CO3 (81.3%). DFT calculations indicate that differing from the pure Bi2O2CO3-catalyzed CO2RR, where formate is formed via a *OCHO intermediate step that requires a high energy input energy of 2.69 eV to proceed, the formation of HCOO− over Bi2O2(CO3) x Cl y has proceeded via a *COOH intermediate step that only requires low energy input of 2.56 eV.

Primulina nana C.Xiong, W.C.Chou & F.Wen, a new species of Gesneriaceae from limestone areas of Guangxi, China, is described and illustrated here. It morphologically resembles P. yangshuoensis Y.G.Wei & F.Wen in papillose leaf surface, but can be easily distinguished from the latter by noting a combination of characteristics, especially in its leaf blades, leaf blade indumentum characteristic, calyx lobes, corolla and the disc. We found only one population at the type locality, about 200 mature individuals. According to the IUCN Red List Categories and Criteria (Version 3.1), the new species is provisionally assessed as Critically Endangered (CR).

Abstract Background Indwelling urethral catheters are widely used in clinical settings. Catheter-associated urinary tract infection has been recognized as a common adverse event in older patients. However, noninfectious complications are almost 5 times as common as infectious complications, and insufficient attention has been given to noninfectious complications. Given this importance, a novel intervention related to removing unnecessary catheters in a timely manner to promote, after removal, the recovery of self-voiding function is herein developed to reduce infectious and noninfectious complications associated with indwelling urethral catheters in hospitalized older patients. Methods A quasi-experimental study design was adopted. Patients aged 65 and older who had a urinary catheter placed within 24 h of hospital admission were included. All patients were allocated into either an intervention group, in which the novel intervention developed in the study was implemented, or a control group, who received care as usual. The outcomes of this study were to evaluate whether the novel intervention reduced the incidence of the following: catheter-associated urinary tract infections, catheter-associated noninfectious complications, decline in activities of daily living, and new nursing home admissions. Results Of 106 hospitalized older patients who consented to participate, 92 completed follow-up until discharge, including 49 in the control group and 43 in the intervention group. The patients in the intervention group were significantly older than those in the control group [83.72 ± 9.18 vs. 80.26 ± 7.66, p = 0.038], and no differences were found between the groups in other demographics or present health conditions. Multivariable logistic regression analysis showed that the control group was more likely to develop noninfectious complications [adjusted odds ratio: 3.01, 95% confidence interval: 1.32–6.81] and a decline in ADLs [adjusted odds ratio: 11.20, 95% confidence interval: 3.68–34.00]. Conclusions A novel intervention can be effective as a means of reducing noninfectious complications associated with indwelling urethral catheters in hospitalized older patients. This approach will help to standardize urethral catheter care, and it highlights the fact that health care professionals can play a crucial role in preventing harm from urethral catheters.

It is difficult to identify and locate the defects quickly when the long cable line cross-bonded box has defects such as grounding,water inflow and three-phase sequence error. Aiming at three types of typical defects of cross-bonded box,a cross-bonded model of long cable lines is established to analyze the amplitude and phase change rule of circulation under the defects. Then,the curve fitting of the ratio of circulation at both ends and the scatter data of defect box number are carried out to obtain the defect location formulas. Finally,it is verified by an example. The results show that the circulation amplitude of the defective phase increases and the non-defective phase is normal when the ground is grounded inside the box. When the phase sequence is wrong,the amplitude of two-phase circulation increases obviously,and the amplitude of the other phase circulation is smaller. When the tank is filled with water,the circulation amplitude of each phase increases and is basically equal. The fitting degree of the positioning formula is about 0.96,and the range of defect box number can be determined through the example verification. The proposed method is not affected by the change of wire core current and ground resistance,and can provide reference for the defect identification and location of long cable line cross-bonded box.

Abstract The formation of gastric cancer (GC) is a complicated process involving multiple factors and multiple steps. The tumor–immune microenvironment is essential for the growth of GC and affects the prognosis of patients. We performed multiple machine learning algorithms to identify immunophenotypes and immunological characteristics in GC patients’ information from the TCGA database and extracted immune genes relevance of the GC immune microenvironment. C-X-C motif chemokine receptor 4 (CXCR4), belongs to the C-X-C chemokine receptor family, which can promote the invasion and migration of tumor cells. CXCR4 expression is significantly correlated to metastasis and the worse prognosis. In this work, we assessed the condition of immune cells and identified the connection between CXCR4 and GC immune microenvironment, as well as the signaling pathways that mediate the immune responses involved in CXCR4. The work showed the risk scores generated by CXCR4-related immunomodulators could distinguish risk groups consisting of differential expression genes and could use for the personalized prognosis prediction. The findings suggested that CXCR4 is involved in tumor immunity of GC, and CXCR4 is considered as a potential prognostic biomarker and immunotherapy target of GC. The prognostic immune markers from CXCR4-associated immunomodulators can independently predict the overall survival of GC.

Abstract Aims Suicidal acts may cluster in time and space and lead to community concerns about further imitative suicidal episodes. Although suicide clusters have been researched in previous studies, less is known about the clustering of non-fatal suicidal behaviour (self-harm). Furthermore, most previous studies used crude temporal and spatial information, e.g., numbers aggregated by month and residence area, for cluster detection analysis. This study aimed to (i) identify space–time clusters of self-harm and suicide using daily incidence data and exact address and (ii) investigate the characteristics of cluster-related suicidal acts. Methods Data on emergency department presentations for self-harm and suicide deaths in Taipei City and New Taipei City, Taiwan, were used in this study. In all-age and age-specific analyses, self-harm and suicide clusters were identified using space–time permutation scan statistics. A cut-off of 0.10 for the p value was used to identify possible clusters. Logistic regression was used to investigate the characteristics associated with cluster-related episodes. Results A total of 5,291 self-harm episodes and 1,406 suicides in Taipei City (2004–2006) and 20,531 self-harm episodes and 2,329 suicides in New Taipei City (2012–2016) were included in the analysis. In the two cities, two self-harm clusters (n [number of self-harm episodes or suicide deaths in the cluster] = 4 and 8 in Taipei City), four suicide clusters (n = 3 in Taipei City and n = 4, 11 and 4 in New Taipei City) and two self-harm and suicide combined clusters (n = 4 in Taipei City and n = 8 in New Taipei City) were identified. Space–time clusters of self-harm, suicide, and self-harm and suicide combined accounted for 0.05%, 0.59%, and 0.08% of the respective groups of suicidal acts. Cluster-related episodes of self-harm and suicide were more likely to be male (adjusted odds ratio [aOR] = 2.22, 95% confidence interval [CI] 1.26, 3.89) and young people aged 10–29 years (aOR = 2.72, 95% CI 1.43, 5.21) than their cluster-unrelated counterparts. Conclusions Space–time clusters of self-harm, suicide, and self-harm and suicide combined accounted for a relatively small proportion of suicidal acts and were associated with some sex/age characteristics. Focusing on suicide deaths alone may underestimate the size of some clusters and/or lead to some clusters being overlooked. Future research could consider combining self-harm and suicide data and use social connection information to investigate possible clusters of suicidal acts.

BackgroundAnlotinib may boost the efficacy of pancreatic cancer (PC) treatment if timely added to the GS regimen (Gemcitabine, Tegafur-gimeracil-oteracil potassium); however, no data has been published. This study evaluated the safety and efficacy of anlotinib in combination with the GS regimen(hereafter referred to as the A+GS regimen) in the first-line treatment of patients with unresectable or metastatic PC.MethodsPatients with unresectable or metastatic PC treated at Yueyang Central Hospital and Yueyang People’s Hospital between October 2018 and June 2022 were enrolled in this retrospective real-world investigation. Treatment efficacy was evaluated based on the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR), while the treatment safety was assessed by the frequency of major adverse events (AEs).ResultsSeventy-one patients were included in this study, 41 in the GS group and 30 in the A+GS group. The A+GS group had a longer mPFS than the GS group (12.0 months (95% CI, 6.0–18.0) and 6.0 months (95% CI, 3.0–8.1)), respectively (P = 0.005). mOS was longer in the GS+A group) when compared with the GS group (17.0 months (95%CI, 14.0–20.0) and 10.0 months (95% CI, 7.5–12.5)), respectively (P = 0.018). The GS+A group had higher ORR (50.0% vs 26.8%, P = 0.045) and DCR (83.3% vs 58.5%, P = 0.026). Furthermore, there were no grade 4-5 AEs and no treatment-related deaths, and no discernible increase in AEs in the GS+A group when compared with the GS group.ConclusionThe A+GS regimen therapy holds great promise in managing treatment-naive advanced PC, except that future prospective studies with larger sample sizes and multiple centers are required to determine its efficacy and safety.

While maintaining information over a delay of time, working memory (WM) also allows individuals to prepare the mnemonic contents for prospective utilisation. However, it remains unclear whether the expectation of the time of WM test could modulate neural responses during the retention interval of WM and subsequent performance. Here, we investigated whether temporal expectations based on the variability of delay duration can modulate 9–13 Hz alpha oscillations during WM retention and whether the expectation-induced alpha activity was associated with WM performance. Participants performed a retro-cueing WM task with magnetoencephalography (MEG) (Experiment 1) and a standard WM task with electroencephalography (EEG) (Experiment 2). The expectation of the timing of the WM test was manipulated by the temporal structure of the tasks with small or large variability in the delay durations. We showed that alpha oscillations during retention interval and WM performance varied with duration variability in both of the MEG and EEG experiments. The novel finding was greater alpha-power attenuation over the left frontal and parietal regions during WM retention when the duration variability was small and the test onset was predictable, compared to when the duration variability was large and the test onset was less predictable. Importantly, we observed a positive relationship in variability difference between the response benefit and alpha-power attenuation in the left posterior parietal regions at both MEG-source and EEG-electrode levels. Finally, we confirmed the behavioural benefit when a condition with a fixed delay-duration was included in a behavioural experiment (Experiment 3). When conjoined, the delay duration enables individuals to anticipate when the relevant information would be put to work, and alpha oscillations track the anticipatory states during WM maintenance.