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Pearl millet is an important cereal crop worldwide and shows superior heat tolerance. Here, we developed a graph-based pan-genome by assembling ten chromosomal genomes with one existing assembly adapted to different climates worldwide and captured 424,085 genomic structural variations (SVs). Comparative genomics and transcriptomics analyses revealed the expansion of the RWP-RK transcription factor family and the involvement of endoplasmic reticulum (ER)-related genes in heat tolerance. The overexpression of one RWP-RK gene led to enhanced plant heat tolerance and transactivated ER-related genes quickly, supporting the important roles of RWP-RK transcription factors and ER system in heat tolerance. Furthermore, we found that some SVs affected the gene expression associated with heat tolerance and SVs surrounding ER-related genes shaped adaptation to heat tolerance during domestication in the population. Our study provides a comprehensive genomic resource revealing insights into heat tolerance and laying a foundation for generating more robust crops under the changing climate.

The inherently dynamic and anisotropic microenvironment of cells imposes not only global and slow physical stimulations on cells but also acute and local perturbations. However, cell mechanical responses to transient subcellular physical signals remain unclear. In this study, acoustically activated targeted microbubbles were used to exert mechanical perturbations to single cells. The cellular contractile force was sensed by elastic micropillar arrays, while the pillar deformations were imaged using brightfield high-speed video microscopy at a frame rate of 1k frames per second for the first 10s and then confocal fluorescence microscopy. Cell mechanical responses are accompanied by cell membrane integrity changes. Both processes are determined by the perturbation strength generated by microbubble volumetric oscillations. The instantaneous cellular traction force relaxation exhibits two distinct patterns, correlated with two cell fates (survival or permanent damage). The mathematical modeling unveils that force-induced actomyosin disassembly leads to gradual traction force relaxation in the first few seconds. The perturbation may also influence the far end subcellular regions from the microbubbles and may propagate into connected cells with attenuations and delays. This study carefully characterizes the cell mechanical responses to local perturbations induced by ultrasound and microbubbles, advancing our understanding of the fundamentals of cell mechano-sensing, -responsiveness, and -transduction. STATEMENT OF SIGNIFICANCE: Subcellular physical perturbations commonly exist but haven't been fully explored yet. The subcellular perturbation generated by ultrasound and targeted microbubbles covers a wide range of strength, from mild, intermediate to intense, providing a broad biomedical relevance. With µm

The change of mechanical properties of the surrounding rock of underground engineering in cold regions decreases engineering safety. In order to explore the influence of fissure angle on the mechanical properties of surrounding rocks, uniaxial compression and acoustic emission tests were carried out on the fissured sandstone in a saturated state. The results showed that the stress-strain curves of the fissured sandstone had “stress drop” phenomena, the acoustic emission ringing count rate and the cumulative ringing count versus time curve could describe the various stages of fissured sandstone failure, and the increase in the fissure angle made the acoustic emission activity more active. Fissures degraded the mechanical properties of sandstone. The peak strength and elastic modulus of the fissured sandstone increased with the increase of the fissure angle due to the large fissure width of the saturated sample and the freezing-thawing effect, and the peak strain and Poisson’s ratio had no obvious regularity. As the fissure angle increased, the dominant cracks in the failure mode changed from tensile cracks to shear cracks and then to tensile cracks, and the failure mode changed from splitting failure to shearing failure and then to splitting failure. This study can provide guidance and suggestions for the design of underground engineering in cold regions.

Protected areas (PAs) are an important estate for sustainable development. Children in PAs are of particular concern, as they are potential future stakeholders of this estate, yet they may be the ones affected the most by the conservation and development programs in PAs. However, knowledge on children in PAs has been very limited, which threatens the probability of the success of both nature conservation and sustainable development. In this paper, we present the findings from a questionnaire survey targeted at schoolchildren in China’s PAs. Our sample consisted of 41 primary schools across China. We looked at 22 indexes of the sample, inferred the conditions in the whole PAs using an exact binomial test, and compared them with those in other rural or urban areas in China. We found that schoolchildren in PAs are substantially disadvantaged in terms of many indexes, both in school and at home. We discuss possible reasons, link these results to Sustainable Development Goals (SDGs), and discuss some policy implications. With this preliminary study, we hope to stimulate additional research on the conditions of children in PAs and their potential implications for sustainable development.

Thiosulfate oxidation by microbes has a major impact on global sulfur cycling. Here, we provide evidence that bacteria within various Roseobacter lineages are important for thiosulfate oxidation in marine biofilms. We isolate and sequence the genomes of 54 biofilm-associated Roseobacter strains, finding conserved sox gene clusters for thiosulfate oxidation and plasmids, pointing to a niche-specific lifestyle. Analysis of global ocean metagenomic data suggests that Roseobacter strains are abundant in biofilms and mats on various substrates, including stones, artificial surfaces, plant roots, and hydrothermal vent chimneys. Metatranscriptomic analysis indicates that the majority of active sox genes in biofilms belong to Roseobacter strains. Furthermore, we show that Roseobacter strains can grow and oxidize thiosulfate to sulfate under both aerobic and anaerobic conditions. Transcriptomic and membrane proteomic analyses of biofilms formed by a representative strain indicate that thiosulfate induces sox gene expression and alterations in cell membrane protein composition, and promotes biofilm formation and anaerobic respiration. We propose that bacteria of the Roseobacter group are major thiosulfate-oxidizers in marine biofilms, where anaerobic thiosulfate metabolism is preferred.

This paper investigates a multi-user multiple-input single-output (MISO) downlink communication system, which is assisted by a dynamic-controlled Reconfigurable Intelligent Surface (RIS). Firstly, we formulate a problem to optimize the active -and passive beamforming matrices with the goal of maximizing the sum rate (SR) of all users under the constraints of Quality of Service (QoS) requirements. A state selection matrix is creatively introduced to control the number of RIS elements used for reflection. And quantized phases are considered in order to be more practical, which is often neglected in existing works. Then, an algorithm based on block coordinate descent (BCD) is proposed to obtain the stationary solution. The algorithm can guarantee the optimal SR regardless of any proportion of closed RIS elements. Finally, we perform simulation verification and analysis the results of the proposed scheme and six baseline schemes. Simulation results show that the proposed scheme is much better than the existing schemes in terms of SR, and realizes good energy efficiency (EE) performance simultaneously. Moreover, the proposed scheme can achieve more significant EE gain by sacrificing less SR.

To develop new strategies for improving the efficacy and biosafety of sonoporation-based macromolecule delivery, it is essential to understand the mechanisms underlying plasma membrane re-sealing and function recovery of the cells perforated by ultrasound-driven microbubbles. However, we lack a clear understanding of the spatiotemporal dynamics of the disrupted actin cytoskeleton and its role in the re-sealing of sonoporated cells. Here we used a customized experimental setup for single-pulse ultrasound (133.33-µs duration and 0.70-MPa peak negative pressure) exposure to microbubbles and for real-time recording of single-cell (human umbilical vein endothelial cell) responses by laser confocal microscopic imaging. We found that in reversibly sonoporated cells, the locally disrupted actin cytoskeleton, which was spatially correlated with the perforated plasma membrane, underwent three successive phases (expansion; contraction and re-sealing; and recovery) to re-model and that each phase of the disrupted actin cytoskeleton was approximately synchronized with that of the perforated plasma membrane. Moreover, compared with the closing time of the perforated plasma membrane, the same time was used for the re-sealing of the actin cytoskeleton in mildly sonoporated cells and a longer time was required in moderately sonoporated cells. Further, the generation, directional migration, accumulation and re-polymerization of globular actin polymers during the three phases drove the re-modeling of the actin cytoskeleton. However, in irreversibly sonoporated cells, the actin cytoskeleton, which underwent expansion and no contraction, was progressively de-polymerized and could not be re-sealed. Finally, we found that intracellular calcium transients were essential for the recruitment of globular actin and the re-modeling of the actin cytoskeleton. These results provide new insight into the role of actin cytoskeleton dynamics in the re-sealing of sonoporated cells and serve to guide the design of new strategies for sonoporation-based delivery.

In this paper, with the aim to enhance the secure transmission and improve the utilization of spectrum resources in IoT, a multicarrier non-orthogonal multiple access (MC-NOMA) assisted full duplex (FD) network is investigated, in which NOMA is implemented in both uplink and downlink transmissions.The lightweight and low-power physical layer security (PLS) technology is employed to protect the information from eavesdropping. Taking the imperfect channel state information (CSI) into account, we formulate a problem to optimize the beamforming vector, artificial noise (AN), transmit power and subcarrier assignment policy aiming to maximize the worst-case sum secrecy rate while subject to the quality of service (QoS) and power consumption constraints. Since the formulated problem is non-convex and difficult to be solved, we decompose it into two joint optimization sub-problems. The first is resource allocation with given subcarrier assignment, which is solved by using the block coordinate descent (BCD) approach. The second is subcarrier assignment solved by matching theory. Our simulation shows that the proposed scheme is robust against the CSI imperfectness of the eavesdropping and self-interference channels, while provides significant sum secrecy rate improvement compared with the OMA, HD systems and other benchmark schemes.

Drought and salinity are major environmental stresses that impair crop growth and productivity worldwide. Improving drought and salt tolerance of crops with microbial mutualists is an effective and environmentally sound strategy to meet the demands of the ever-growing world population. In the present study, we found that the Streptomyces albidoflavus OsiLf-2, a moderately salt-tolerant endophytic actinomycete, produced abundant osmolytes, including proline, polysaccharides, and ectoine. Inoculation with OsiLf-2 increased the osmotic-adjustment ability of the rice host by increasing the proline content (by 250.3% and 49.4%) and soluble sugar (by 20.9% and 49.4%) in rice under drought and salt conditions, relative to the uninoculated control. OsiLf-2 increased stress responses in the rice host at the physiological and biochemical levels (photosynthesis efficiency, osmolytes and antioxidant content), and the gene level (osmolytes synthesis, stress-responsive and ion-transport related genes), raising rice yields under both greenhouse and saline–alkaline soil conditions. The use of endophytic actinomycetes offers a promising biotechnological approach to developing stress-tolerant plants.

Information on previous treatment of patients included in the observational study.LTIL-01.

The compositions of the sorted PD-1- and PD-1+ fraction prior to expansion. Upper panel: PD-1 negative fraction; Lower panel: PD-1 positive fraction. (n=9)

Pie graph shows the composition of TIL samples of MM-3.

Information on previous treatment of patients included in the observational study.LTIL-04.

Additional information on patients included in Figure 1-5.

Information on previous treatment of patients included in the observational study.LTIL-03.

The accumulative frequency of shared TIL clones in TCR-β repertoire of PD-1+ T from patient MM-4 before and after in vitro expansion.

Both tumor-infiltrating lymphocytes (TIL) and PD-1+ peripheral blood lymphocytes (PBL) are enriched for tumor-reactive clones recognizing known and unknown tumor antigens. However, the relationship between the T-cell receptor-β (TCRβ) repertoires of the TILs and T cells expanded from paired PD-1+ PBLs, and whether T cells expanded from PD-1+ PBLs can be used to treat patients with cancer as TIL substitutes remain unclear. Here, we established a highly efficient protocol to prepare polyclonal T cells from PD-1+ PBLs. A functional T-cell assay and tetramer staining revealed that cells from PD-1+ PBLs were relatively enriched for tumor-reactive T cells. Furthermore, deep TCRβ sequencing data revealed that an average of 11.29% (1.32%–29.06%; P = 0.015; n = 8) tumor-resident clonotypes were found in T cells expanded from paired PD-1+ PBLs, and the mean accumulated frequency of TIL clones found in T cells expanded from PD-1+ PBLs was 35.11% (7.23%–78.02%; P = 0.017; n = 8). Moreover, treatment of four patients, who failed multiline therapy and developed acquired resistance to anti-PD-1, with autologous T cells expanded from PD-1+ PBLs combined with anti-PD-1 antibody elicited objective responses from three of them. These results indicate that T cells expanded from PD-1+ PBLs share more clones with paired TILs and could be used to treat patients with cancer as TIL substitutes.Significance:This study harnesses the tumor reactivity of PD-1+ PBLs, developing a method to expand T cells from these clones as a potential therapeutic strategy and TIL substitute in patients with cancer.See related commentary by Ladle, p. 1940

Box plot shows the percentage of CD45RA-CD62L+, CD45RA- CD62L-, CD45RA+ CD62L+, and CD45RA+ CD62L- T cells in the subset of CD4+ (A and E, PD-1-T cells; B and F, PD-1+T cells )and CD8+ (C and G, PD-1-T cells; D and H, PD-1+T cells ) T cells before (Upper panel, n=4) and after (Lower panel, n=8) expansion with the protocol established in this study.

Information on previous treatment of patients included in the observational study.LTIL-02.

Grain chalkiness is an important index of rice appearance quality and is negatively associated with rice processing and eating quality. However, the genetic mechanism underlying chalkiness formation is largely unknown. To identify the genetic basis of chalkiness, 410 recombinant inbred lines (RILs) derived from two representative indica rice varieties, Shuhui498 (R498) and Yihui3551 (R3551), were used to discover quantitative trait loci (QTLs). The two parental lines and RILs were grown in three locations in China under three controlled fertilizer application levels. Analyses indicated that chalkiness was significantly affected by genotype, the environment, and the interaction between the two, and that heritability was high. Several QTLs were isolated, including the two stable QTLs qCGP6 and qCGP8. Fine mapping and candidate gene verification of qCGP6 showed that Wx may play a key role in chalkiness formation. Chromosomal segment substitution lines (CSSLs) and near-isogenic lines (NILs) carrying the Wxa or Wxin allele produced more chalky grain than the R498 parent. A similar result was also observed in the 3611 background. Notably, the effect of the Wx genotype on rice chalkiness was shown to be dependent on environmental conditions, and Wx alleles exhibited different sensitivities to shading treatment. Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), the Wxa promoter region was successfully edited; down-regulating Wx alleviates chalkiness formation in NILR498-Wxa. This study developed a new strategy for synergistic improvement of eating and appearance qualities in rice, and created a novel Wx allele with great potential in breeding applications.

BackgroundData on drug-coated balloons (DCB) for de novo coronary chronic total occlusion (CTO) are limited. We aimed to investigate the long-term outcomes of substitution of drug-eluting stents (DES) by DCB.MethodsWe compared the outcomes of less DES strategy (DCB alone or combined with DES) and DES-only strategy in treating de novo coronary CTO in this prospective, observational, multicenter study. The primary endpoints were major adverse cardiovascular events (MACE), target vessel revascularization, myocardial infarction, and death during 3-year follow-up. The secondary endpoints were late lumen loss (LLL) and restenosis until 1-year after operation.ResultsOf the 591 eligible patients consecutively enrolled between January 2015 and December 2019, 281 (290 lesions) were treated with DCB (DCB-only or combined with DES) and 310 (319 lesions) with DES only. In the DCB group, 147 (50.7%) lesions were treated using DCB-only, and the bailout stenting rate was relatively low (3.1%). The average stent length per lesion in the DCB group was significantly shorter compared with the DES-only group (21.5 ± 25.5 mm vs. 54.5 ± 26.0 mm, p p p p > 0.999). The Kaplan–Meier estimates of MACE at 3-year (11.8% vs. 12.0%, log-rank p = 0.688) was similar between the groups.ConclusionPercutaneous coronary intervention with DCB is a potential “stent-less” therapy for de novo CTO lesions with satisfactory long-term clinical results compared to the DES-only approach.

Mountainous scenic spots are important tourism resources, and the study of tourists’ landscape perception and emotional preference when visiting them is beneficial to the management of scenic spots in order to improve the service quality and promote the protection, development, and utilization of scenic resources. In this paper, we use the location photo data of tourists at Huangshan Mountain to extract the visual semantic information of location photos, calculate the photo sentiment value, and mine the landscape perception and sentiment preference features of tourists using DeepSentiBank image recognition model and photo visual semantic quantification method. The results show the following: (1) Huangshan tourists mainly focus on nine types of photos, with the most attention paid to the category of mountain rock landscapes and the least attention paid to the category of animal landscapes. (2) In terms of spatial distribution, the landscape types of tourist photos show the spatial characteristics of “concentrated into a belt”, “significant nucleus”, and “fragmented distribution”. The spatial variation of the emotional value of tourists’ photos is significant, and the high values are mainly distributed at the entrances and exits, interchanges, and famous attractions. (3) On a temporal scale, the type of perception of the Huangshan location photograph landscape shows a significant imbalance. The emotional values of tourists’ photos vary significantly, with a “slowly sloping straight line” type of emotional change on the seasonal scale, a “W” type of emotional change on the monthly scale, an “N” type of emotional change on the weekly scale, and an “M” type of emotional change on the hourly scale. This study attempts to explore the landscape perceptions and emotional preferences of tourists in mountainous scenic areas with new data and methods, aiming to promote the sustainable and high-quality development of mountainous scenic areas.

BackgroundCognitive impairment is one of the common sequelae after stroke, which not only hinders the recovery of patients but also increases the financial burden on families. In the absence of effective therapeutic measures, acupuncture treatment has been widely used in China to treat post-stroke cognitive impairment (PSCI), but the specific efficacy is unclear. Therefore, this review aimed to evaluate the true efficacy of acupuncture treatment in patients with PSCI.MethodsWe searched eight databases [PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China Biomedical Literature Database (CBM), China Science and Technology Journal (VIP) database, the China National Knowledge Infrastructure (CNKI) database, and Wan fang database] from the inception to May 2022 for randomized controlled trials (RCTs) related to acupuncture treatment combined with cognitive rehabilitation (CR) for PSCI. Two investigators independently used a pre-designed form to extract valid data from eligible RCTs. The risk of bias was assessed through tools provided by the Cochrane Collaboration. The meta-analysis was implemented through Rev Man software (version 5.4). The strength of the evidence obtained was evaluated using GRADE profiler software. Adverse events (AEs) were collected by reading the full text and used to evaluate the safety of acupuncture treatment.ResultsThirty-eight studies involving a total of 2,971 participants were included in this meta-analysis. Overall, the RCTs included in this meta-analysis were poor in methodological quality. The combined results showed that acupuncture treatment combined with CR showed significant superiority compared to CR alone in terms of improving cognitive function [Mean Difference (MD) = 3.94, 95% confidence intervals (CI): 3.16–4.72, P < 0.00001 (MMSE); MD = 3.30, 95%CI: 2.53–4.07, P < 0.00001 (MoCA); MD = 9.53, 95%CI: 5.61–13.45, P < 0.00001 (LOTCA)]. Furthermore, the combination of acupuncture treatment and CR significantly improved patients' self-care ability compared to CR alone [MD = 8.66, 95%CI: 5.85–11.47, P < 0.00001 (MBI); MD = 5.24, 95%CI: 3.90–6.57, P < 0.00001 (FIM)]. Meanwhile, subgroup analysis showed that MMSE scores were not sufficiently improved in the comparison of electro-acupuncture combined with CR versus CR alone (MD = 4.07, 95%CI: −0.45–8.60, P = 0.08). However, we also observed that electro-acupuncture combined with CR was superior to the use of CR alone in improving MoCA and MBI scores in patients with PSCI [MD = 2.17, 95%CI: 0.65–3.70, P = 0.005 (MoCA); MD = 1.74, 95%CI: 0.13–3.35, P = 0.03 (MBI)]. There was no significant difference in the occurrence of adverse events (AE) between acupuncture treatment combined with CR and CR alone (P > 0.05). The certainty of the evidence was rated low level because of flaws in the study design and considerable heterogeneity among the included studies.ConclusionThis review found that acupuncture treatment combined with CR may have a positive effect on improving cognitive function and self-care ability in PSCI patients. However, our findings should be treated with caution owing to the existence of methodological quality issues. High-quality studies are urgently required to validate our results in the future.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022338905, identifier: CRD42022338905.

Background The incidence of postoperative nausea and vomiting (PONV) after laparoscopic sleeve gastrectomy (LSG) is up to 80% in China, and the current antiemetic means is mainly the use of antiemetics. This is a randomized, controlled, single-blind study to evaluate the safety and efficacy of auricular acupressure (AA) after LSG. Methods A multicenter, randomized, controlled, single-blind, superiority trial (RCT) was designed, and the relevant ethics committee approved the trial protocol. This study used AA as the experimental group and the control group act as a blank group. The primary evaluation index was the INVR score. The secondary indexes were time to first postoperative bed release, time to first anal defecation and time to return to fluid intake after surgery. A total of one hundred patients who met the inclusion and exclusion criteria were randomly grouped, and baseline measurements and outcome indicators were assessed preoperatively and postoperatively, respectively. Discussion This trial is a standardized, scientific clinical trial designed to evaluate the effect of AA on the degree of relief of nausea and vomiting and recovery of gastrointestinal function after LSG. We expect the study to provide a basis for promoting this therapy in clinical practice. Trial registration Chinese Clinical Trial Registry, ChiCTR2100047381, registered on 13 June 2021.http://www.chictr.org.cn/showproj.aspx?proj=49359

In this paper, a convenient process for the fabrication of flexible liquid metal mesh films (LMMF) is proposed first. Then, the light transmittance and square resistance characteristics of LMMF are studied theoretically and experimentally. The light transmittance of the LMMF can reach 85% when the line width and spacing are 50 μm and 1000 μm, respectively. Furthermore, as an example of LMMF, a coplanar waveguide loop antenna is designed and fabricated that contains an LMMF with a line width of 50 μm and a line spacing of 500 μm. The measured square resistance and transmittance for the LMMF are 0.0456 Ω/sq and 72%, respectively. The measured peak gain of the antenna is 3.38 dBi while the average efficiency is 61%. The antenna’s working frequency covers most of the S-band, C-band, and X-band, as well as multiple channels of fifth generation (5G) communication. Therefore, the antenna can be used in fields such as radar and mobile communication. Uniquely, the fabricated antenna performs well in terms of light transmission, conductivity, and flexibility. In particular, it remains stable in stretching and bending deformation. As a highly light-transmissive stretchable flexible antenna, the antenna is equipped with various functions such as concealability, conformability, and reconfigurability. This LMMF-based antenna has good prospects for applications in the fields of flexible electronics and transparent electronics.