Search

Abstract Functional traits reflect plants' adaptability to their environment, and environmental gradients influence their distribution. But few studies have investigated the link between these traits and species substitution patterns or the relevant ecological factors. We measured the aboveground (leaf) and belowground (root) functional traits of Stipa species in 17 plots across natural grasslands in Ningxia in Northern China. Redundancy analysis was used to explore the relationships between Stipa's functional traits and its species substitution distribution. Then, on the species substitution gradient, principal component analysis (PCA) was used to verify and quantify the leaf economic spectrum (LES), root economic spectrum (RES), and whole‐plant economic spectrum (WPES), with the relation between these spectra investigated by fitting standardized major axis regressions. The effects of aboveground, belowground, and whole‐plant ecological factors were quantified and ranked by variance decomposition and hierarchical partitioning. Our results showed that functional traits drive the substitution distribution of Stipa species, in being variously coupled with its desert, typical, and meadow steppe habitat types. The leaf, root, and whole‐plant economic spectra of Stipa species in desert steppe exhibit a “quick investment‐acquisition” strategy. In typical steppe, the leaf and whole‐plant economic spectra of Stipa species correspond to a “fast investment‐acquisition” strategy, whereas the root economic spectrum adopts a “slow investment‐acquisition” strategy. On meadow steppe, the leaf, root, and whole‐plant economic spectra of Stipa species similarly adopt a “slow investment‐acquisition” strategy. Finally, when considering the environmental factors involved, we find that the substitution distribution of Stipa spp. is chiefly a response to shifting soil patterns, these mainly driven by soil total nitrogen and nitrogen/phosphorus ratio. Collectively, these findings provide an important reference for the ecological restoration and reconstruction of grassland ecosystems, to better understand the relationship between plant functional traits and ecological niche attributes, and thus guide the reasonable restoration of grassland vegetation.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Objective A micro‐electromechanical system (MEMS) was developed based on spatial alignment and navigation technology to assist femoral extramedullary alignment osteotomy (FEAO) in total knee arthroplasty (TKA). The system can locate and adjust the femoral distal condylar osteotomy (FDCO) to obtain a better femoral prosthesis placement. It is a portable navigation device and provides an innovative approach for FDCO. Methods Sixty patients who suffered from severe knee osteoarthritis who underwent unilateral TKA from May 14, 2021 to May 30, 2022 were randomly divided into a MEMS‐FEAO group and a conventional femoral intramedullary alignment osteotomy (FIAO) group, with 30 cases in each group for a controlled retrospective study. The hip‐knee‐ankle angle (HKAA) of the lower limb was measured before and after surgery, the femoral valgus angle (FVA) was measured preoperatively, and the femoral prosthesis valgus angle (FPVA) and the femoral prosthesis flexion angle (FPFA) were measured postoperatively following computed tomography imaging protocols. Measurement data is statistically described as mean ± standard deviation c. The count data is described by frequency (constituent ratio) using the rank sum test. Result A total of 6.7% (2/30) of FEAO compared to 20.0% (6/30) of FIAO cases were postoperative deviations where the HKAA exceeded ±3° of neutral alignment (p 0.05), and there was no statistical significance between the two groups. Conclusion The MEMS‐FEAO system can improve the accurate alignment and can be utilized as a locator to obtain the best femoral prosthesis placement in TKA and significantly reduce the rate of poor force line of the lower limb.

Key Clinical Message Maternally inherited diabetes and deafness (MIDD) is often caused by the m.3243A > G mutation in mitochondrial DNA. Unfortunately, the characteristics of MIDD, especially long‐term outcomes and heteroplasmic changes, have not been well described previously. The purpose of this study was to describe the clinical and genetic features of a family with MIDD after 10 years of follow‐up.A 33‐year‐old male patient with typical characteristics of MIDD, including early‐onset diabetes, deafness, and low body mass index, was admitted to our department. Further investigation revealed that the vast majority of his maternal relatives suffered from diabetes with or without deafness. A detailed family history was then requested from the patient and a pedigree was constructed. The patient suspected of MIDD was screened for mutations using whole mitochondrial DNA sequencing. Candidate pathogenic variants were then validated in other family members through Sanger sequencing. The patient was diagnosed with MIDD, with inherited m.3243A > G mutation in the mitochondrially encoded tRNA leucine 1 (MT‐TL1) gene, after 10 years of symptom onset. The patient was then treated with insulin and coenzyme Q10 to improve mitochondrial function. During the follow‐up period, his fasting blood glucose and HbA1c levels were improved and the incidence of diabetic ketoacidosis was significantly reduced. Our findings indicate that whole mitochondrial DNA sequencing should be considered for patients suspected of MIDD to improve the efficiency of diagnosis and prognosis.

Abstract Objective To date, epigenetic studies identified differential DNA methylation (DNAm) related to gestational‐body mass index (BMI) in offspring at birth. This study investigated whether the identified DNAm in offspring were also associated with BMI trajectories from infancy to age 26 years. Methods Data of 794 participants from Isle of Wight birth cohort in UK were investigated to study association between BMI trajectories and DNAm related to gestational‐BMI at birth. Multinominal logistic regression models were applied to test the association between 1090 DNAm sites reported in three prior epigenome‐wide association studies and BMI trajectories. Results DNAm site cg23089913 (NANOS1) and cg13217064 (SOX14) were associated with early persistent obesity (EPO) and delayed overweight (DOW) trajectories respectively. A higher methylation of cg23089913 showed low odds of being in EPO trajectory (OR: 0.84; 95% CI: 0.76–0.93) while higher methylation of cg13217064 resulted in 1.4‐times the odds of being in DOW trajectory when compared to the normal trajectory [Correction added on 22 February 2023, after first online publication: Range of the DNAm site cg23089913 has been changed from ‘lower’ to ‘higher’ in the preceding sentence.]. In a gender‐stratified analysis, the odds of developing into DOW was 1.8 times in female participants for cg13217064 while not such association was observed in males. Conclusions Deviations in methylation of cg23089913 (NANOS1) and cg13217064 (SOX14) in newborns may change the risk of having excess body weight.

Abstract The controllable synthesis of complicated nanostructures in advanced two‐dimensional (2D) semiconductors, such as periodic regular hole arrays, is essential and remains immature. Here, we report a green, facile, highly controlled synthetic method to efficiently pattern 2D semiconductors, such as periodic regular hexagonal‐shaped hole arrays (HHA), in 2D‐TMDs. Combining the production of artificial defect arrays through laser irradiation with anisotropic annealing etching, we created HHA with different arrangements, controlled hole sizes, and densities in bilayer WS2. Atomic force microscopy (AFM), Raman, photoluminescence (PL), and scanning transmission electron microscopy (STEM) characterization show that the 2D semiconductors have high quality with atomical clean and sharp edges as well as undamaged crystals in the unetched region. Furthermore, other nanostructures, such as nanoribbons and periodic regular triangular‐shaped 2D‐TMD arrays, can be fabricated. This kind of 2D semiconductors fabrication strategy is general and can be extended to a series of 2D materials. Density functional theory (DFT) calculations show that one WS2 molecule from the edges of the laser‐irradiated holed region exhibits a robust etching activation, making selective etching at the artificial defects and the fabrication of regular 2D semiconductors possible.

Abstract Heterotopic ossification (HO) is a double‐edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material‐induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material‐induced bone formation. Hypoxia inducible factor‐1α (HIF‐1α), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF‐1α significantly inhibits M2 macrophage, subsequent osteoclast, and material‐induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast‐conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF‐1α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid‐loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.

Prognosticating the efficacy of anti‐angiogenic therapy through longitudinal monitoring and early detection of treatment resistance in cancer patients remain highly challenging. In this study, co‐detection and comprehensive phenotypic and karyotypic molecular characterization of aneuploid circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) were conducted on non‐small cell lung cancer (NSCLC) patients receiving bevacizumab plus chemotherapy. Prognostic values of the cell‐based significant univariate risk factors identified by Cox regression analyses were progressively investigated. Subjects showing an increase in total post‐therapeutic platelet endothelial cell adhesion molecule‐1 (CD31)– CTCs and CD31+ CTECs exhibited a significantly reduced median progression‐free survival (mPFS) and overall survival. Further stratification analyses indicated that pretherapeutic patients bearing vimentin (Vim)+ CTECs (mesenchymal M‐type) at baseline revealed a significantly shortened mPFS compared with patients with Vim– CTECs. Post‐therapeutic patients harboring epithelial cell adhesion molecule (EpCAM)+ CTCs and CTECs (epithelial E‐type), regardless of Vim expression or not, showed a significantly reduced mPFS. Post‐therapeutic patients possessing de novo EpCAM+/Vim+ (hybrid E/M‐type) CTECs displayed the shortest mPFS. Patients harboring either pre‐ or post‐therapeutic EpCAM–/Vim– null CTECs (N‐type) exhibited a better response to therapy compared to patients harboring EpCAM+ and/or Vim+ CTECs. The presented results support the notion that baseline Vim+ CTECs and post‐therapeutic EpCAM+ CTCs and CTECs are predictive biomarkers for longitudinal monitoring of response to anti‐angiogenesis combination regimens in NSCLC patients.

Abstract The two‐dimensional (2D) in‐plane (lateral) heterostructures have attracted increasing interest for potential applications in the atomically thin electronics and optoelectronics. While most studies focus on semiconductor‐semiconductor lateral heterostructures with highly similar lattice structures between the constituent components, the synthesis of metal‐semiconductor lateral heterostructures is much less explored and usually more challenging due to more distinct lattice structures or chemical properties. Herein, a vapor phase epitaxy growth method of high‐quality metal‐semiconductor lateral heterostructures between tetragonal CoSe and hexagonal WSe2 is reported. The 2D CoSe can selectively nucleate at the edge of pre‐grown WSe2 nanosheets to form CoSe‐WSe2 metal‐semiconductor lateral heterostructures. Optical microscopy (OM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) studies reveal distinct contrast across the heterostructure interface. High‐resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) studies further confirm the microstructure modulation across the heterostructure interface. The field‐effect transistors (FETs) of CoSe‐WSe2 lateral heterostructures show satisfactory Ohmic contacts and considerably better FET performance over those with deposited Cr/Au contacts, suggesting the in‐plane metal‐semiconductor junctions may function as improved contacts for the atomically thin electronics.

Abstract The hierarchically lithiated MoO3 microspheres composed of primary crystallized particles have been prepared in the absence of surfactant. The surface morphologies of the lithiated MoO3 structures can be well regulated through adjusting the adding amounts of ethanol during their synthetic process. The results of XRD patterns and the elemental analysis indicated the decrease of lithium content with the increase of ethanol feeding amount. The obtained lithiated MoO3 samples showed the initial capacities of nearly 300 mAh/g at 30 mA/g and 41.8 mAh/g at 200 mA/g. Therefore, this work has showed a facile way to fabricate the lithiated MoO3 cathode materials with controllable surface morphology and lithium content.

Abstract Thickness‐dependent chemical and physical properties have gained tremendous interest since the emergence of two‐dimensional (2D) materials. Despite attractive prospects, the thickness‐controlled synthesis of ultrathin nanosheets remains an outstanding challenge. Here, a chemical vapor deposition (CVD) route is reported to controllably synthesize high‐quality PtSe2 nanosheets with tunable thickness and explore their thickness‐dependent electronic and magnetotransport properties. Raman spectroscopic studies demonstrate all Eg, A1g, A2u, and Eu modes are red shift in thicker nanosheets. Electrical measurements demonstrate the 1.7 nm thick nanosheet is a semiconductor with room temperature field‐effect mobility of 66 cm2 V−1 s−1 and on/off ratio of 106. The 2.3–3.8 nm thick nanosheets show slightly gated modulation with high field‐effect mobility up to 324 cm2 V−1 s−1 at room‐temperature. When the thickness is over 3.8 nm, the nanosheets show metallic behavior with conductivity and breakdown current density up to 6.8 × 105 S m–1 and 6.9 × 107 A cm−2, respectively. Interestingly, magnetoresistance (MR) studies reveal magnetic orders exist in this intrinsically non‐magnetic material system, as manifested by the thickness‐dependent Kondo effect, where both metal to insulator transition and negative MR appear upon cooling. Together, these studies suggest that PtSe2 is an intriguing system for both developing novel functional electronics and conducting fundamental 2D magnetism study.

To evaluate whether heart rate variability (HRV) as a measure of cardiac autonomic neuropathy (CAN) is associated with chronic kidney disease (CKD) in Chinese adults with type 2 diabetes mellitus (T2DM) in China. 392 individuals of T2DM were entered in this study, all these subjects undertook the Holter electrocardiogram for 24 hours to get the HRV parameters. Of these T2DM patients, 126 (37.3%) had CKD, and most of the HRV parameters were lower in this group than in those without CKD. Decreased HRV parameters were strongly related with CKD in Spearman’s correlation analysis. After adjustments for variables, the logistic regression showed that standard deviation of the averaged normal RR intervals for all 5-minute segments (SDANN) was independently associated with decreased estimated glomerular filtration rate (eGFR

Abstract Aging is a critical factor affecting physical health and disease in mammals. Emerging evidence indicates that aging may affect the gut bacteriome in cynomolgus macaques, but little is known about whether or how the gut virome changes with age. Here, we compared the DNA gut viral composition of 16 female cynomolgus monkeys (Macaca fascicularis) at three life stages (young, adult, and old) using the shotgun metagenome sequencing method. We found that the DNA gut virome from these monkeys differed substantially among the three groups. The gut viruses were dominated by bacteriophages, the most abundant of which was the Caudovirales order (i.e., Siphoviridae, Myoviridae, and Podoviridae families). Additionally, the co‐occurrence analysis revealed that the age‐related bacteriophages were correlated in an extensive and complex manner with the main intestinal bacteria (i.e., Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla). Furthermore, the age‐related DNA gut viral functions were enriched for genetic information processing, nucleotide, and folate metabolism. Our gut virome analysis provides new insight into how aging influences the gut virome of non‐human primates.

There could be an overlap of monogenic diabetes and early-onset type 2 diabetes mellitus. Precise diagnosis of early-onset diabetes has proven valuable for understanding the mechanism of diabetes and selecting optimal therapy. The majority of maturity onset diabetes of the young (MODY) pathogenic genes in China is still unknown. In this study, a family with suspected MODY was enrolled. Whole-exome sequencing (WES) was used to analyze the variants of the proband. Variants were filtered according to their frequency, location, functional consequences, and bioinformatics software. Candidate pathogenic variants were validated by Sanger sequencing and tested for cosegregation in other members of the family and nonrelated healthy controls. KEGG (Kyoto Encyclopedia of Genes and Genomes) and PPI (protein-protein interaction) analysis were conducted using the DAVID (Database for Annotation, Visualization, and Integrated Discovery) and the STRING online analysis tools for the candidate pathogenic gene. A total of 123291 variants including 105344 SNPs and 17947 InDels were found in WES. A likely pathogenic rare missense heterozygous mutation in diabetes genes (c.2137C > T, p.His713Tyr in IRS1) was identified, which was a cosegregate in this family and not in nonrelated healthy controls. The position of the mutation in the aminoacid sequence of the gene is highly conserved among the species. 2 significantly enriched KEGG pathways were identified including bta04930, type II diabetes mellitus (GCK, INS, PDX1, ABCC8, and IRS1), and bta04910, insulin signaling pathway (GCK, INS, and IRS1). PPI analysis displayed that IRS1 interacts with 3 known pathogenic proteins including INS, KCNJ11, and GCK. We conclude that WES could be an initial option for genetic testing in patients with early-onset diabetes. IRS1 p.His713Tyr is implicated as a possible pathogenic mutation in monogenic diabetes, which might require further validation, and the precise molecular mechanism underlying the influence of IRS1 p.His713Tyr on the development of diabetes remains to be determined in the further prospective studies.

We proposed an approach that has the ability to detect spatial clusters with skewed or irregular distributions. A mixture of Dirichlet processes (DP) was used to describe spatial distribution patterns. The effects of different batches of data collection efforts were also modeled with a Dirichlet process. To cluster spatial foci, a birth-death process was applied due to its advantage of easier jumping between different numbers of clusters. Inferences of parameters including clustering were drawn under a Bayesian framework. Simulations were used to demonstrate and assess the method. We applied the method to an fMRI meta-analysis dataset to identify clusters of foci corresponding to different emotions.

BIPV is now widely used in office and residential buildings, but its seismic performance still remained vague especially when the photovoltaic (PV) modules are installed on high-rise building facades. A new form of reinforced concrete shear wall integrated with photovoltaic module is proposed in this paper, aiming to apply PV module to the facades of high-rise buildings. In this new form, the PV module is integrated with the reinforced concrete wall by U-shaped steel connectors through embedded steel plates. The lateral cyclic loading test is executed to investigate the seismic behavior and the electric and thermal performance with different drift angles. The seismic behavior, including failure pattern, lateral force-top displacement relationship, and deformation capacity, was investigated. The power generation and temperature variation on the back of the PV module and both sides of the shear wall were also tested. Two main results are demonstrated through the experiment: (1) the U-shaped steel connectors provide enough deformation capacity for the compatibility of the PV module to the shear wall during the whole cyclic test; (2) the electricity generation capacity is effective and stable during this seismic simulation test.

Singularity problem exists in various branches of applied mathematics. Such ordinary differential equations accompany singular coefficients. In this paper, by using the properties of reproducing kernel, the exact solution expressions of dual singular problem are given in the reproducing kernel space and studied, also for a class of singular problem. For the binary equation of singular points, I put it into the singular problem first, and then reuse some excellent properties which are applied to solve the method of solving differential equations for its exact solution expression of binary singular integral equation in reproducing kernel space, and then obtain its approximate solution through the evaluation of exact solutions. Numerical examples will show the effectiveness of this method.

Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n=930) and European Americans (EA, n=993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50–0.97 and OR = 0.61; 95% CI, 0.40–0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23–0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35–0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men.

African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973–2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7–38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7–19.8). These rates were considerably lower than those of 80.0–195.3 observed among African Americans. Rates in Africa increased over time (1987–2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa.