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Abstract Cadmium (Cd) is a high‐risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd‐induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd‐induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP‐response element binding protein at Ser133(CREBS133) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage‐dependent anion‐selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity.

Rumination is closely related to mental disorders and can thus be used as a marker of their presence or a predictor of their development. The presence of masking and fabrication in psychological selection can lead to inaccurate detection of psychological disorders. Human language is considered crucial in eliciting specific conscious activities, and the use of natural language processing (NLP) in the development of questionnaires for psychological tests has the potential to elicit immersive ruminative thinking, leading to changes in neural activity. Electroencephalography (EEG) is commonly used to detect and record neural activity in the human brain and is sensitive to changes in brain activity. In this study, we used NLP to develop a questionnaire to induce ruminative thinking and then recorded the EEG signals in response to the questionnaire. The behavioral results revealed that ruminators exhibited higher arousal rates and longer reaction times, specifically in response to the ruminative items of the questionnaire. The EEG results showed no significant difference between the ruminators and the control group during the resting state; however, a significant alteration in the coherence of the entire brain of the ruminators existed while they were answering the ruminative items. No differences were found in the control participants while answering the two items. These behavioral and EEG results indicate that the questionnaire elicited immersive ruminative thinking, specifically in the ruminators. Therefore, the questionnaire designed using NLP is capable of eliciting ruminative thinking in ruminators, offering a promising approach for the early detection of mental disorders in psychological selection.

The synthesis of two-dimensional lateral heterojunctions with nanoscale characteristic width and sharp interfaces remains challenging. The quantum confinement effects are still difficult to create on 2D materials since widths smaller than 5 nm are necessary for quantum confinement effects and quantum well applications. In this study, we demonstrated the growth of a sub-2-nm tungsten sulfide quantum well array in a monolayer of tungsten selenide, driven by the climb of mismatch dislocation in a heterointerface due to the lattice mismatch. Width-controllable 2D quantum well superlattices are theoretically formed by the mismatch dislocation-driven growth mechanism, according to our analysis. Thus, abundant photonic electronic properties can be obtained in 2D quantum well superlattices formed at varied lateral heterointerfaces, which will support the study of topological insulators and superconductors.

Exhausted shallow resources have turned mining into deep mining, with the mining depth of most mines under construction being more than 1000 m. With the continuous increase of the mining depth of mineral resources, the thickness and strength grade of the shaft lining concrete increases, resulting in higher hydration heat. The freezing method is usually used in deep well construction, resulting in a high temperature on one side and a low temperature on the other side of the shaft wall concrete. The influence law of this environment on concrete needs to be studied. It is of great theoretical significance for deep well construction and service safety to find out the change law of the shaft wall concrete performance under a freezing construction environment. The temperature difference between −5/60 ℃ and −5/70 ℃ was applied to simulate the state of the mass concrete in the freezing method construction environment. The ultrasonic parameters, compressive strength, splitting tensile strength, chloride diffusion coefficient, and bursting liability of concrete under the simulated environment were studied, and the scanning electron microscope of the concrete was analyzed. Results show that the freezing construction environment will cause certain damage to the interior of the concrete, and the damage parallel to the heating direction is greater than that in the vertical direction. The damage of the C50 concrete is greater than that of the C70 concrete, and the temperature gradient will aggravate the internal damage of the concrete. The simulated freezing environment will have adverse effects on the compressive strength, splitting tensile strength, chloride ion permeability, and bursting liability of the concrete. The temperature difference has a positive correlation with the performance reduction rate, which becomes more significant for low-strength concrete. The internal microstructure of the concrete block is uneven due to the simulated freezing environment, the concrete structure at the low-temperature end is loose, and the structure at the high-temperature end is dense, resulting in the decrease of the concrete’s performance.

Cellulose is the most abundant renewable biomass raw material in nature and has great potential to solve the energy crisis. However, the comprehensive utilization rate of cellulose is low due to its complex structure, which is difficult to degrade. The degradation of cellulose by microorganism is an important strategy to realize its recycling. The microbial degradation of cellulose is reviewed from three aspects, including single strain, complex flora and optimized combination of isolates. The advantages and application values of each screening strategy are summarized and analyzed. Moreover, the microbial degradation mechanism and future development of cellulose are described to give opportunities for exploring new ideas of more efficient cellulose degradation.

Abstract Objectives To explore the feasibility of two‐port robotic sleeve lobectomy using Stratafix sutures for central lung tumors, and to summarize the surgical techniques and clinical outcomes. Methods We retrospectively evaluated 15 consecutive patients who underwent robotic bronchial sleeve lobectomy, performed by a single surgeon between March 2021 and September 2021. A half‐continuous suture technique with two Stratafix sutures was used for bronchial anastomosis. The operative techniques and outcomes were analyzed. Results Complete resection was achieved in all patients undergoing different types of robotic bronchial sleeve lobectomy. There were no conversions to thoracotomy. The mean duration of surgery was 102.35 ± 46.31 min, mean time for bronchial anastomosis was 25.8 ± 15.2 min, mean blood loss was 64.71 ± 38.59 ml, and mean postoperative hospital stay was 4.76 ± 2.54 days. There was no death on follow‐up within 90 days after surgery. Conclusions Two‐port robotic bronchial sleeve lobectomy and the novel anastomotic technique are both feasible and safe for selected patients.

ObjectiveTo examine the equity in human resources allocation in centers for disease prevention and control (CDCs) and to provide evidences for optimizing resource allocation. Methods The data on human resources among CDCs in all administrative regions across China in 2014 and 2019 were collected from China′s Statistical Yearbook of Health and Family Planning – 2015 and China′s Statistical Yearbook of Health – 2020. Then, health resource agglomeration degree (HRAD) was used to evaluate the equity in human resources allocation according to population and geographical area. Results The total number of personnel in CDCs across China decreased by 2.51% from 192 397 in 2014 to 187 564 in 2019. The number of CDCs′ personnel per 10 000 population also showed a shrinking trend at all provincial levels and the number for most provincial level regions did not meet the national standard. In 2019, the proportions of CDC personnel at young age (< 35 years) and middle-aged (35 – 54 years) decreased by 3.8% and 2.4% compared with those in 2014, but the proportion of elderly personnel (≥ 55 years) increased by 6.0% contrasting to that in 2014. The number of personnel with high school/technical secondary school education or below in all CDCs in China decreased from 28.8% in 2014 to 19.4% in 2019, while the number of those with junior college education or above increased from 71.1% in 2014 to 80.6% in 2019. The results of analysis on the equity in human resources allocation showed that the spatial distribution of human resource was unbalanced. The geographical region-specific HRAD index was the highest (indicating a better equity in human resources allocation) for eastern region, followed by that for central and western region; while, the population distribution-specific HRAD index was higher for western region than that for central and eastern region. Conclusion Insufficient total number, serious turnover and unbalanced allocation are main problems in health resources allocation for CDCs in China and the situation needs to be improved for CDCs′ capability construction in China.

Introduction: The SARS-CoV-2 pandemic has endangered global health, the world economy, and societal values. Despite intensive measures taken around the world, morbidity and mortality remain high as many countries face new waves of infection and the spread of new variants. Worryingly, more and more variants are now being identified, such as 501Y.V1 (B.1.1.7) in the UK, 501Y.V2 (B.1.351) in South Africa, 501Y.V3 in Manaus, Brazil, and B.1.617/B.1.618 in India, which could lead to a severe epidemic rebound. Moreover, some variants have a stronger immune escape ability. To control the new SARS-CoV-2 variant, we may need to develop and redesign new vaccines repeatedly. So it is important to investigate how our immune system combats and responds to SARS-CoV-2 infection to develop safe and effective medical interventions. Objectives: In this study, we performed a longitudinal and proteome-wide analysis of antibodies in the COVID-19 patients to revealed some immune processes of COVID-19 patients against SARS-CoV-2 and found some dominant epitopes of a potential vaccine. Methods: Microarray assay, Antibody depletion assays, Neutralization assay. Results: We profiled a B-cell linear epitope landscape of SARS-CoV-2 and identified the epitopes specifically recognized by either IgM, IgG, or IgA. We found that epitopes more frequently recognized by IgM are enriched in non-structural proteins. We further identified epitopes with different immune responses in severe and mild patients. Moreover, we identified 12 dominant epitopes eliciting antibodies in most COVID-19 patients and identified five key amino acids of epitopes. Furthermore, we found epitope S-82 and S-15 are perfect immunogenic peptides and should be considered in vaccine design. Conclusion: This data provide useful information and rich resources for improving our understanding of viral infection and developing a novel vaccine/neutralizing antibodies for the treatment of SARS-CoV-2.

Abstract To effectively solve the problem of dust pollution caused by the parallel double-belt transportation of coal in a coal preparation plant, taking the Huangyuchuan coal preparation plant as an example, a numerical model of the air flow-dust distribution was established by means of simulation. The flow lines between the strips of tape and the tail of the tape machine will gather, and there will be backflow on the right side of the 3001 tape and left side of the 3002 tape. Under the action of wind current, most of the dust particles larger than 10 μm are distributed in the range of 0–5 m on both sides of the tape; dust particles smaller than 10 μm spread to the entire preparation workshop. Combined with field test verification, dust pollution is mainly concentrated at the guide trough, the feed inlet, the rear of the machine, and the joint of the belt corridor. Based on this, a targeted spray dust reduction treatment plan is proposed. By measuring the dust concentration before and after the treatment of dust-polluted areas, it is proven that the dust reduction efficiency of this plan can reach more than 90%.

Endocrine therapy has become the fundamental treatment option for hormone receptor-positive (HR+) and receptor tyrosine-protein kinase erbB-2-negative (HER2-) metastatic breast cancer (mBC). While treatments incorporating cyclin-dependent kinase (CDK)4 and 6 inhibitors are more prevalent than ever, comparisons among those regimens are scarce. The aim of the present study was to identify the most effective maintenance treatment for patients with HR+ and HER2- mBC. To this end, databases including PubMed, Embase, Cochrane Library, Scopus and Google Scholar were searched from inception to August, 2023. The endpoints comprised overall survival (OS) and progression free survival (PFS). For dichotomous variants, hazard ratios (HRs) and odds ratios (ORs) were generated, while standard mean difference (SMD) was used for consecutive variants by Bayesian network meta-analysis to make pairwise comparisons among regimens, to determine the optimal therapy. These processes were conducted using Rstudio 4.2.2 orchestrated with STATA 17.0 MP. A total of 16 randomized controlled trials including 7,174 patients with 11 interventions were analyzed. Compared with aromatase inhibitor (AI), palbociclib plus AI (PalboAI) exhibited a significantly longer PFS up to the 36th month of follow-up [HR=1.7; 95% credible interval, 1.36-2.16], including on the 3rd [OR=2.22; 95% confidence interval (CI), 1.10-4.47], 6th (OR=2.39; 95% CI, 1.21-4.69), 12th (OR=1.94; 95% CI, 1.34-2.79), 18th (OR=2.38; 95% CI, 1.65-3.44), 24th (OR=2.39; 95% CI, 1.67-3.43), 30th (OR=2.10; 95% CI, 1.62-2.74) and 36th (OR=2.66; 95% CI, 1.37-5.18) month of follow-up. Additionally, abemaciclib plus fulvestrant exhibited significant effects compared with AI alone between 12 and 36 months. Ribociclib plus fulvestrant, ribociclib plus AI and dalpiciclib plus AI exerted significant effects compared with AI alone between 12 and 30 months. Considering the effect on OS and PFS together with adverse reactions, safety, medical compliance and route of administration, PalboAI was found to be the optimal treatment for HR+/HER2-mBC. However, additional head-to-head clinical trials are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

In this study, we present a ligand-free nickel(II)-catalyzed halogen exchange of aromatic halides with magnesium chloride. This method effectively facilitates the retro-Finkelstein reaction for a wide range of aryl bromides, iodides and triflates, demonstrating excellent functional group tolerance. Mechanistic studies reveal that magnesium plays a crucial role in the challenging reductive elimination from Ni(II) intermediates. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-1 (HIV-1) infection disrupts the homeostatic equilibrium between the host and commensal microbes. However, the dynamic changes of plasma commensal viruses and their role in HIV/simian immunodeficiency virus (SIV) pathogenesis are rarely reported. Here, we investigated the longitudinal changes of plasma virome, inflammation levels, and disease markers using an SIV-infected Macaca leonina model. Large expansions of plasma Anelloviridae, Parvoviridae, Circoviridae and other commensal viruses, and elevated levels of inflammation and D-dimer were observed since the chronic phase of SIV infection. Anelloviridae abundance appears to correlate positively with the CD4+ T cell count but negatively with SIV load especially at the acute phase, whereas other commensal viruses' abundances show opposite correlations with the two disease markers. Antiretroviral therapy slightly reduces but does not substantially reverse the expansion of commensal viruses. Furthermore, 1387 primate anellovirus open reading frame 1 sequences of more than 1500 nucleotides were annotated. The data reveal different roles of commensal viruses in SIV pathogenesis. [ABSTRACT FROM AUTHOR]

The manuscript introduces a new structural system called the reinforced concrete (RC) space grid cassette multi-tube structure for high-rise buildings. A case study building is analyzed using this system and compared to a conventional RC frame-core tube structure. Through modal analysis in the software "Midas Gen", the torsional effect and control indices like inter-story displacement ratio, maximum displacement, etc. are compared between the two structural systems. The results show that the space grid cassette system has smaller displacement ratios, displacements, inter-story torsion angles, and thus better torsional resistance compared to the conventional frame-core tube system. Based on these analyses, the manuscript concludes that the RC space grid cassette multi-tube structural system has superior seismic performance and is more suitable for irregularly shaped high-rise residential buildings. [ABSTRACT FROM AUTHOR]

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy. [ABSTRACT FROM AUTHOR]

Sorafenib, a kinase inhibitor, has shown promising therapeutic efficacy in a subset of patients with acute myeloid leukemia (AML). However, despite its clinical effectiveness, sorafenib resistance is frequently observed in clinical settings, and the mechanisms underlying this resistance as well as effective strategies to overcome it remain unclear. We examined both single-cell and bulk transcription data in sorafenib-resistant and control AML patients and integrated a sorafenib resistance gene signature to predict the sensitivity of AML cells and the clinical outcomes of AML patients undergoing sorafenib therapy. In addition, our drug sensitivity analysis of scRNA-seq data using deconvolution methods showed that venetoclax was effective in targeting sorafenib-resistant AML cells. Mechanistically, sorafenib was found to activate the JAK-STAT3 pathway and upregulate BCL2 expression in sorafenib-resistant AML cells. This upregulation of BCL2 expression rendered the cells vulnerable to the BCL2 inhibitor venetoclax. In conclusion, we developed a platform to predict sorafenib resistance and clinical outcomes in AML patients after therapy. Our findings suggest that the combination of sorafenib and venetoclax could be an effective therapeutic strategy for AML treatment.

Abstract Background Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo. Methods LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD. Results We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption. Conclusions These results showed that TOD can be adopted as a potential therapeutic agent for OA.

Abstract Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

Abstract Background Diabetic retinopathy (DR) has become a leading cause of global blindness as a microvascular complication of diabetes. Regular screening of diabetic retinopathy is strongly recommended for people with diabetes so that timely treatment can be provided to reduce the incidence of visual impairment. However, DR screening is not well carried out due to lack of eye care facilities, especially in the rural areas of China. Artificial intelligence (AI) based DR screening has emerged as a novel strategy and show promising diagnostic performance in sensitivity and specificity, relieving the pressure of the shortage of facilities and ophthalmologists because of its quick and accurate diagnosis. In this study, we estimated the cost-effectiveness of AI screening for DR in rural China based on Markov model, providing evidence for extending use of AI screening for DR. Methods We estimated the cost-effectiveness of AI screening and compared it with ophthalmologist screening in which fundus images are evaluated by ophthalmologists. We developed a Markov model-based hybrid decision tree to analyze the costs, effectiveness and incremental cost-effectiveness ratio (ICER) of AI screening strategies relative to no screening strategies and ophthalmologist screening strategies (dominated) over 35 years (mean life expectancy of diabetes patients in rural China). The analysis was conducted from the health system perspective (included direct medical costs) and societal perspective (included medical and nonmedical costs). Effectiveness was analyzed with quality-adjusted life years (QALYs). The robustness of results was estimated by performing one-way sensitivity analysis and probabilistic analysis. Results From the health system perspective, AI screening and ophthalmologist screening had incremental costs of $180.19 and $215.05 but more quality-adjusted life years (QALYs) compared with no screening. AI screening had an ICER of $1,107.63. From the societal perspective which considers all direct and indirect costs, AI screening had an ICER of $10,347.12 compared with no screening, below the cost-effective threshold (1–3 times per capita GDP of Chinese in 2019). Conclusions Our analysis demonstrates that AI-based screening is more cost-effective compared with conventional ophthalmologist screening and holds great promise to be an alternative approach for DR screening in the rural area of China.

Abstract Osteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole “organ” including cartilage, subchondral bone, synovium, and muscles. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the pathogenesis of age-related diseases including OA. In this review, we mainly focus on the role of the senescent skeletal cells (chondrocytes, osteoblasts, osteoclasts, osteocyte, and muscle cells) in initiating the development and progression of OA alone or through cross-talk with the macrophages/synovial cells. Accordingly, we summarize the current OA-targeted therapies based on the abovementioned theory, e.g., by eliminating senescent skeletal cells and/or inhibiting the senescence-associated secretory phenotype (SASP) that drives senescence. Furthermore, the existing animal models for the study of OA from the perspective of senescence are highlighted to fill the gap between basic research and clinical applications. Overall, in this review, we systematically assess the current understanding of cellular senescence in OA, which in turn might shed light on the stratified OA treatments.

Permanent-magnet materials are critical components for green energy technologies, but the intrinsic trade-off between saturation magnetization and coercivity limits their achievable energy density. Here, a new concept of ordered structures is proposed to develop high-performance permanent magnets. This strategy enables a rare combination of high magnetization and high coercivity by introducing new magnetization reversal mechanisms associated with ordered structures. Implications and challenges of building ordered structures for strong magnets are discussed. This Perspective aims to draw the attention of materials research community to the emerging ordered magnets and to motivate active investigations on this topic for creating transformative magnets.

Abstract Background Cultivated peanut (Arachis hypogaea, AABB genome), an allotetraploid from a cross between A. duranensis (AA genome) and A. ipaensis (BB genome), is an important oil and protein crop with released genome and RNA-seq sequence datasets. These datasets provide the molecular foundation for studying gene expression and evolutionary patterns. However, there are no reports on the proteomic data of A. hypogaea cv. Tifrunner, which limits understanding of its gene function and protein level evolution. Results This study sequenced the A. hypogaea cv. Tifrunner leaf and root proteome using the tandem mass tag technology. A total of 4803 abundant proteins were identified. The 364 differentially abundant proteins were estimated by comparing protein abundances between leaf and root proteomes. The differentially abundant proteins enriched the photosystem process. The number of biased abundant homeologs between the two sub-genomes A (87 homeologs in leaf and root) and B (69 and 68 homeologs in leaf and root, respectively) was not significantly different. However, homeologous proteins with biased abundances in different sub-genomes enriched different biological processes. In the leaf, homeologs biased to sub-genome A enriched biosynthetic and metabolic process, while homeologs biased to sub-genome B enriched iron ion homeostasis process. In the root, homeologs with biased abundance in sub-genome A enriched inorganic biosynthesis and metabolism process, while homeologs with biased abundance in sub-genome B enriched organic biosynthesis and metabolism process. Purifying selection mainly acted on paralogs and homeologs. The selective pressure values were negatively correlated with paralogous protein abundance. About 77.42% (24/31) homeologous and 80% (48/60) paralogous protein pairs had asymmetric abundance, and several protein pairs had conserved abundances in the leaf and root tissues. Conclusions This study sequenced the proteome of A. hypogaea cv. Tifrunner using the leaf and root tissues. Differentially abundant proteins were identified, and revealed functions. Paralog abundance divergence and homeolog bias abundance was elucidated. These results indicate that divergent abundance caused retention of homologs in A. hypogaea cv. Tifrunner.

A decade ago the first rare-earth-metal dependent enzyme was discovered, in which a non-redox lanthanide ion is central in the active site of a methanol dehydrogenase. Inspired by this discovery, here the authors show that an open-shell semi-quinone anionic radical species, complexed with lanthanum, could serve as a very efficient aerobic oxidation catalyst under ambient conditions.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Abstract Transmission lines are affected by aeolian vibration, sandstorms and acid rain, which cause structural damage and eventually lead to line breaking accidents. In this paper, the structural health monitoring technology of conductors is researched, and a structural monitoring system for conductors is designed. First, based on the structure of the ACSR (Aluminum Conductor Steel Reinforced) conductor and the dynamic equation, the relation between the natural frequencies and the structure of the conductor is obtained. Then, an online health monitoring system of the conductor structure is proposed, and key issues, such as the power supply solution of sensors, data preprocessing technology, multiple‐sensor synchronization method, are analyzed in detail. Finally, the structural health monitoring of overhead transmission lines designed in this paper is tested on 110‐kV experimental transmission lines. The experimental results show that from the system proposed the operation parameters of the conductors can be well obtained.

Optical metasurfaces, i.e., thin planar structures with subwavelength metal or dielectric unit cells, have attracted great interest due to their intriguing capabilities of shaping light in both linear and nonlinear regimes. However, their saturable absorption properties and corresponding applications have so far been rarely exploited. Here we report on passively mode-locked ytterbium-doped fiber lasers utilizing saturable metasurfaces made of periodically arranged gold nanorods. Three 400-nm-period metasurfaces with gold nanorods of different lengths (from 210 to 240 nm) and plasmonic resonances (from 968 to 1044 nm) are fabricated and found to exhibit nonlinear absorption with decent modulation depths, facilitating the formation of mode-locking states at 1060 nm. The corresponding lasers generate typically mode-locked pulses with the duration of ∼ 62.3 ps, repetition rate of 10.33 MHz, and signal-to-noise ratio of ∼74 dB. Our experimental results demonstrate that the gold nanorod-based metasurfaces can be used as relatively broadband mode-lockers in the 1-μm-wavelength range.

IntroductionWith the COVID-19 pandemic in China, a large number of mild or ordinary confirmed cases have been sent to Fangcang shelter hospitals for treatment. We aimed to investigate the mental health condition of Fangcang patients 2 years after the pandemic when patients knew more about COVID-19 and the virus was less virulent. We focused on the effect of dysfunctional beliefs and attitudes about sleep on depression, anxiety, and insomnia.MethodsA total of 1,014 patients from two large Fangcang shelter hospitals in Shanghai between 22 April and 8 May 2022 completed a set of questionnaires comprising: the Dysfunctional Beliefs and Attitudes about Sleep scale, the Generalized Anxiety Disorder scale, the Patient Health Questionnaire, and the Insomnia Severity Index scale.ResultsResults show that the positive screening rates for anxiety, depression, and insomnia among tested patients were 55.3, 27.0, and 47.8%, respectively. Patients were more likely to report higher anxiety, depression, and insomnia, and to endorse affective and sleep disorders if they were: female, aged 18–40 years, with undergraduate course or above, white-collar employees, or those who thought the pandemic would have severe economic effects. About 51.4% of the participants had dysfunctional beliefs about sleep to varying degrees. Compared with patients who had accurate beliefs about sleep, the ratios of insomnia, anxiety, and depression were significantly higher among patients with dysfunctional beliefs about sleep.DiscussionAttention should be paid to the mental health problems of patients in Fangcang shelter hospitals. The results indicate that dysfunctional beliefs about sleep significantly increased anxiety, depression, and insomnia of Fangcang patients.

Alternative polyadenylation (APA) is a molecular process that generates diversity at the 3’ end of RNA polymerase II transcripts from over 60% of human genes. APA and microRNA regulation are both mechanisms of post-transcriptional regulation of gene expression. As a key molecular mechanism, Alternative polyadenylation often results in mRNA isoforms with the same coding sequence but different lengths of 3’ UTRs, while microRNAs regulate gene expression by binding to specific mRNA 3’ UTRs. Nudix Hydrolase 21 (NUDT21) is a crucial mediator involved in alternative polyadenylation (APA). Different studies have reported a dual role of NUDT21 in cancer (both oncogenic and tumor suppressor). The present review focuses on the functions of APA, miRNA and their interaction and roles in development of different types of tumors.NUDT21 mediated 3’ UTR-APA changes can be used to generate specific signatures that can be used as potential biomarkers in development and disease. Due to the emerging role of NUDT21 as a regulator of the aforementioned RNA processing events, modulation of NUDT21 levels may be a novel viable therapeutic approach.

IntroductionSeed dormancy (SD) significantly decreases under high temperature (HT) environment during seed maturation, resulting in pre-harvest sprouting (PHS) damage under prolonged rainfall and wet weather during wheat harvest. However, the molecular mechanism underlying HT-mediated SD remains elusiveSeed dormancy (SD) significantly decreases under high temperature (HT) environment during seed maturation, resulting in pre-harvest sprouting (PHS) damage under prolonged rainfall and wet weather during wheat harvest. However, the molecular mechanism underlying HT-mediated SD remains elusive.MethodsHere, the wheat landrace ‘Waitoubai’ with strong SD and PHS resistance was treated with HT from 21 to 35 days post anthesis (DPA). Then, the seeds under HT and normal temperature (NT) environments were collected at 21 DPA, 28 DPA, and 35 DPA and subjected to whole-transcriptome sequencing.ResultsThe phenotypic data showed that the seed germination percentage significantly increased, whereas SD decreased after HT treatment compared with NT, consistent with the results of previous studies. In total, 5128 mRNAs, 136 microRNAs (miRNAs), 273 long non-coding RNAs (lncRNAs), and 21 circularRNAs were found to be responsive to HT, and some of them were further verified through qRT-PCR. In particular, the known gibberellin (GA) biosynthesis gene TaGA20ox1 (TraesCS3D02G393900) was proved to be involved in HT-mediated dormancy by using the EMS-mutagenized wheat cultivar Jimai 22. Similarly, a novel gene TaCDPK21 (TraesCS7A02G267000) involved in the calcium signaling pathway was validated to be associated with HT-mediated dormancy by using the EMS mutant. Moreover, TaCDPK21 overexpression in Arabidopsis and functional complementarity tests supported the negative role of TaCDPK21 in SD. We also constructed a co-expression regulatory network based on differentially expressed mRNAs, miRNAs, and lncRNAs and found that a novel miR27319 was located at a key node of this regulatory network. Subsequently, using Arabidopsis and rice lines overexpressing miR27319 precursor or lacking miR27319 expression, we validated the positive role of miR27319 in SD and further preliminarily dissected the molecular mechanism of miR27319 underlying SD regulation through phytohormone abscisic acid and GA biosynthesis, catabolism, and signaling pathways.DiscussionThese findings not only broaden our understanding of the complex regulatory network of HT-mediated dormancy but also provide new gene resources for improving wheat PHS resistance to minimize PHS damage by using the molecular pyramiding approach.

Purpose: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI. Experimental design: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated paired pre- and post-irradiation patient rectal adenocarcinoma samples underwent WES. Results: Irradiated-L tumors showed increased tumor mutational burden (TMB) and a sustained decrease in ITH. Irradiated-L tumors were predicted to express five neoantigens with high variant allele frequency/clonal distribution. Mice with irradiated-L and irradiated-H versus parental B16F10 tumors demonstrated longer overall survival with dual ICI. Only mice with irradiated-L tumors experienced an overall survival benefit with single agent ICI. Clinically correlated rectal adenocarcinoma samples showed similarly increased TMB and decreased ITH following irradiation. Conclusions: Post-irradiation ITH modulates ICI response in a murine melanoma model. Irradiation may offer a mechanism to widen the therapeutic window of ICI.

Cotton boll count is an important phenotypic trait that aids in a better understanding of the genetic and physiological mechanisms of cotton growth. Several computer vision technologies are available for cotton boll segmentation. However, estimating the number of cotton bolls in a segmented cluster of cotton bolls is a challenging task due to the complex shapes of cotton bolls. This study proposed a combination of spectral-spatial and supervised machine learning based methods for cotton boll candidate recognition and counting from high resolution RGB images obtained from unmanned aerial vehicles (UAVs). An algorithm consisting of machine vision, band-mean filter, Otsu thresholding, red/blue band ratio filter, and geometrical characteristics-based error removal techniques, was employed to detect open cotton boll pixels under several environmental settings. In addition, a support vector machine (SVM) based encoding method was developed using geometric features of cotton boll candidates to predict the number of cotton bolls from the segmented cotton boll candidates. This algorithm was implemented over three experiment sites with three cotton varieties, two tillage practices, seven cover crop treatments, two irrigation regimes (irrigated and rainfed), 26 irrigation levels, and two sensors (DJI FC6310 RGB and MicaSense Rededge) capturing images at two spatial resolutions (0.75 cm and 1.07 cm) over two growing seasons (2019 and 2021). These different experimental settings allowed the proposed approaches to be validated against a variety of complex backgrounds. A visual inspection of 1000 randomly selected pixels revealed that the proposed cotton boll candidate recognition approach was highly effective in segmenting cotton bolls and background pixels, with high classification accuracy (> 95%) and a low number of falsely classified pixels (precision > 0.96; recall > 0.93). A high correlation between ground truth observations and predicted cotton boll count indicated that the use of geometric features of segmented candidates as predictors in association with the SVM model demonstrated a good performance in estimating boll count from recognized cotton boll candidates. Furthermore, linear regression analyses revealed that both boll count and candidate area are potential predictors of lint yield, with boll count being a better predictor than candidate area. Overall, the study demonstrated that machine vision/learning techniques can be potentially used on UAV images to count the number of cotton bolls and predict lint yield over large acreages with reasonable accuracy.