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Abstract Materials exhibiting a significant shift current response could potentially outperform conventional solar cell materials. The myriad of factors governing shift-current response, however, poses significant challenges in finding such strong shift-current materials. Here we propose a general design principle that exploits inter-orbital mixing to excite virtual multiband transitions in materials with multiple flat bands to achieve an enhanced shift current response. We further relate this design principle to maximizing Wannier function spread as expressed through the formalism of quantum geometry. We demonstrate the viability of our design using a 1D stacked Rice-Mele model. Furthermore, we consider a concrete material realization - alternating angle twisted multilayer graphene (TMG) - a natural platform to experimentally realize such an effect. We identify a set of twist angles at which the shift current response is maximized via virtual transitions for each multilayer graphene and highlight the importance of TMG as a promising material to achieve an enhanced shift current response at terahertz frequencies. Our proposed mechanism also applies to other 2D systems and can serve as a guiding principle for designing multiband systems that exhibit an enhanced shift current response.

Abstract Background Sedentary behavior (SB) is deeply ingrained in the daily lives of community-dwelling older adults with type 2 diabetes mellitus (T2DM). However, the specific underlying mechanisms of the determinants associated with SB remain elusive. We aimed to explore the determinants of SB based on the behavior change wheel framework as well as a literature review. Methods This cross-sectional study recruited 489 community-dwelling older adults with T2DM in Jinan City, Shandong Province, China. Convenience sampling was used to select participants from relevant communities. This study used the Measure of Older Adults’ Sedentary Time-T2DM, the Abbreviated-Neighborhood Environment Walkability Scale, the Social Support Rating Scale, the Lubben Social Network Scale 6, the Subjective Social Norms Questionnaire for Sedentary Behavior, the Functional Activities Questionnaire, the Numerical Rating Scale, the Short Physical Performance Battery, and the Montreal Cognitive Assessment Text to assess the levels of and the determinants of SB. Descriptive statistical analysis and path analysis were conducted to analyze and interpret the data. Results Pain, cognitive function, social isolation, and social support had direct and indirect effects on SB in community-dwelling older adults with T2DM (total effects: β = 0.426, β = -0.171, β = -0.209, and β = -0.128, respectively), and physical function, walking environment, and social function had direct effects on patients’ SB (total effects: β = -0.180, β = -0.163, and β = 0.127, respectively). All the above pathways were statistically significant (P

Abstract Spinal cord malignant melanotic schwannoma (MMNST) is a rare central nervous system tumor that originates from the spinal cord or spinal myelin sheath cells and can produce melanin. This type of tumor is usually highly aggressive and malignant, with a poor prognosis. The clinical manifestations of spinal cord MMNST are mainly pain, paresthesia, muscle weakness, muscle atrophy, etc., and symptoms of spinal cord compression, such as intestinal and bladder dysfunction, paraplegia, etc. Early detection of tumor lesions can facilitate tumor removal, improve patients’ quality of life, and prolong patients’ survival. In this case report, a 27-year-old young woman was diagnosed with MMNST of the cervical spinal cord due to weakness of her limbs in our hospital, and underwent surgical resection. The patient’s limbs returned to normal after surgery. It is worth mentioning that the patient visited our hospital 7 months ago for “right upper limb pain for 3 days” and was diagnosed with a cervical spine space-occupying lesion at the same position this time, but the pathology report was “hemosiderosis”. This case report aims to raise awareness of the problem of spinal cord MMNST and contribute to greater knowledge of this rare tumor.

Abstract Nowadays, the paradigm of mobile computing is evolving from a centralized cloud model towards Mobile Edge Computing (MEC). In regions without ground communication infrastructure, incorporating aerial edge computing nodes into network emerges as an efficient approach to deliver Artificial Intelligence (AI) services to Ground Devices (GDs). The computation offloading and resource allocation problem within a HAP-assisted MEC system is investigated in this paper. Our goal is to minimize the energy consumption. Considering the randomness and dynamism of the task arrival of GDs and the quality of wireless communication, stochastic optimization techniques are utilized to transform the long-term dynamic optimization problem into a deterministic optimization problem. Subsequently, the problem is further decomposed into three sub-problems which can be solved in parallel. An online Energy Efficient Dynamic Offloading (EEDO) algorithm is proposed to address these problems. Then, we conduct the theoretical performance analysis for EEDO. Finally, we carry out parameter analysis and comparative experiments, demonstrating that the EEDO algorithm can effectively reduce system energy consumption while maintaining the stability of the system.

Abstract Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme -/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1β, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

Endangered species generally have small populations with low genetic diversity and a high genetic load. Thuja sutchuenensis is an endangered conifer endemic to southwestern China. It was once considered extinct in the wild, but in 1999 was rediscovered. However, little is known about its genetic load. We collected 67 individuals from five wild, isolated T. sutchuenensis populations, and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in T. sutchuenensis to delineate the conservation units of T. sutchuenensis, based on whole transcriptome sequencing data, as well as target capture sequencing data. We found that populations of T. sutchuenensis could be divided into three groups. These groups had low levels genetic diversity and were moderately genetically differentiated. Our findings also indicate that T. sutchuenensis suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial Maximum. Among Thuja species, T. sutchuenensis presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying selection. However, distribution of fitness effects analysis indicated a high extinction risk for T. sutchuenensis. Multiple lines of evidence identified three management units for T. sutchuenensis. Although T. sutchuenensis possesses a low genetic load, low genetic diversity, suboptimal fitness, and anthropogenic pressures all present an extinction risk for this rare conifer. This might also hold true for many endangered plant species in the mountains all over the world.

Summary: The European-centered genome-wide association studies of schizophrenia (SCZ) may not be well applied to non-European populations. We analyzed 1,592 reported SCZ-associated genes using the public genome data and found an overall higher Asian-European differentiation on the SCZ-associated variants than at the genome-wide level. Notable examples included 15 missense variants, a regulatory variant SLC5A10-rs1624825, and a damaging variant TSPAN18-rs1001292. Independent local adaptations in recent 25,000 years, after the Asian-European divergence, could have contributed to such genetic differentiation, as were identified at a missense mutation LTN1-rs57646126-A in Asians, and a non-risk allele ZSWIM6-rs72761442-G in Europeans. Altai-Neanderthal-derived alleles may have opposite effects on SCZ susceptibility between ancestries. Furthermore, adaptive introgression was detected on the non-risk haplotype at 1q21.2 in Europeans, while in Asians it was observed on the SCZ risk haplotype at 3p21.31 which is also potentially ultra-violet protective. This study emphasizes the importance of including more representative Asian samples in future SCZ studies.

Abstract Purpose While coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, millions of patients with COVID-19 have recovered and returned to their families and work, although the key factors of sequela-free survival remain unknown. Here we determine key factors associated with sequela-free survival of patients with COVID-19. Methods Sequela-free survival is defined as having none of the long-term sequelae measured with the Activity of Daily Living (ADL) Scale, modified Medical Research Council (mMRC) Dyspnoea Scale, New York Heart Association (NYHA) classification, Self-rating Depression Scale (SDS), Carcinologic Handicap Index (CHI) and Modified Telephone Interview for Cognitive Status (TICS-M). Multivariable logistic regression was used to examine the key factors of sequela-free survival. Results The follow-up period for the 464 patients was 10 August to 30 September 2020. Of these, 424 patients completed the assessment of all scales. 30.2% (128 of 424) were categorised as sequela-free at follow-up. The most common sequelae were psychosocial problems (254 [57.7%]), respiratory function abnormality (149 [32.6%]) and cardiac function abnormality (98 [21.5%]). Risk factors associated with COVID-19 sequelae were anaemia on admission, longer duration from the onset of symptoms to admission and increasing of age, whereas anaemia treatment was a protective factor against sequelae. A haemoglobin level of

Abstract Gasdermin D (GSDMD)-mediated pyroptosis has a significant pro-inflammation characteristic due to dramatic secretion of pro-inflammatory substances. However, its role remains unclear in psoriasis as one chronic inflammatory skin disorder with high prevalence. We found that N-terminal GSDMD (N-GSDMD) was aberrantly expressed in epidermis of skin lesion in psoriasis patients and imiquimod-induced psoriasis-like dermatitis (IIPLD) mice. In epidermis of IIPLD mice and M5 (simulating psoriatic inflammatory challenge)-treated keratinocytes cultured in vitro, cleavage products of caspase-1, GSDMD and IL-1β were increased. M5-stimulated keratinocyte presented typical pyroptosis morphology accompanied with PI-staining. Gsdmd −/− keratinocytes could not present pyroptosis morphology while stimulated with M5. Electroporation of recombinant N-GSDMD could make the pyroptosis morphology reappear. In Gsdmd −/− mice or keratinocyte-specific Gsdmd conditional knockout mice, we observed the alleviation of psoriatic inflammation and epidermal aberrant expression of Ki-67 and differentiation markers (loricrin and keratin 5) after imiquimod stimulation. Transplanting skin tissue from control mice to Gsdmd −/− mice can evoke the response to imiquimod stimulation in the background of Gsdmd −/− mice (not limited in transplanting area). In M5-stimulated keratinocytes, disulfiram or GSDMD siRNA transfection can inhibit pyroptosis and eliminate disproportionate increases of Ki-67 and PI. We further validated that topically application of disulfiram (pyroptosis inhibitor) also alleviated IIPLD in mice. These findings indicate a novel mechanism that GSDMD-mediated keratinocyte pyroptosis facilitates hyperproliferation and aberrant differentiation induced by immune microenvironment in psoriatic skin inflammation, which contributes to pathogenesis of psoriasis. Our study provides an innovative insight that targeting pyroptosis can be considered as a therapeutic strategy against psoriasis.

Traditionally, many researchers have supported a uniformitarian view whereby all languages are of roughly equal complexity, facilitated by internal trade-offs between complexity at different levels, such as morphology and syntax. The extent to which the speakers' societies influence the trade-offs has not been well studied. In this paper, we focus on morphology and syntax, and report significant correlations between specific linguistic and societal features, in particular those relating to exoteric (open) vs. esoteric (close-knit) society types, characterizable in terms of population size, mobility, communication across distances, etc. We conduct an exhaustive quantitative analysis drawing upon WALS, D-Place, Ethnologue and Glottolog, finding some support for our hypothesis that languages spoken by exoteric societies tend towards more complex syntaxes, while languages spoken by esoteric societies tend towards more complex morphologies.

The hypothesis that all languages are equally complex often invokes a trade-off principle, according to which if a language is more complex in one particular domain, it will be simpler in another different domain. In this paper, we use data from WALS to test the existence of a trade-off between two specific domains: morphology and syntax. Contrary to widespread views, we did not find a negative correlation between these two language domains, but in fact a positive correlation. At the same time, this positive correlation seems to be driven by some language families, and it disappears when one considers purely morphological and purely syntactic features only. We discuss these findings in relation to ongoing research about language complexity, and in particular, the effects of factors external to language on linguistic structure.

Energy distribution justice is of primary concern within the energy justice framework and it is crucial to increase public acceptance of offshore wind energy and further advance its development. The rapid development of offshore wind energy in China has inevitably impacted the livelihoods of coastal vulnerable groups (CVGs) engaged in fisheries and tourism in the coastal zone. While current policies often compensate for livelihood losses through cash payments, the fiscal strain caused by COVID-19 renders this approach unsustainable. Consequently, this research pioneers the exploration of Chinese tourist groups’ landscape preferences towards offshore wind farms (OWFs). This study proposes a new approach to enhance OWF landscapes for tourism development, thereby balancing the distribution of costs and benefits between CVGs and tourists. The research focuses on Beihai City in the Beibu Gulf Economic Region, utilizing a combination of Q-methodology and choice experiments that incorporates cut-offs. Answers to eighty Q-methodology questionnaires and 1324 choice experiment questionnaires are obtained. The findings indicate that this region can achieve energy distribution justice by compensating for the livelihood losses of CVGs through tourism. Contrary to traditional assumptions about wind farm noise preferences, Chinese tourists prefer proximity to OWFs, as an appropriate coastal acoustics landscape can enhance their tourism experience. In light of these findings, this paper presents policy recommendations towards energy distribution justice.

Abstract Keratinocyte necroptosis (with proinflammatory characteristic) is required for epidermal damage in contact hypersensitivity (CHS). In DNCB-induced CHS mice model, we observed the aggravated keratinocyte death and increased phosphorylation level of MLKL, RIPK3 and RIPK1. However, CHS skin lesion did not present in keratinocyte-specific Mlkl knockout mice. We validated that MLKL-mediated keratinocyte necroptosis is required for epidermal damage in response to immune microenvironment in CHS. Moreover, MLKL-mediated necroptosis deficiency or inhibition resulted in blocking recruitment and activation of inflammatory cells in CHS via reducing HMGB1 release in keratinocytes. This study suggests that MLKL-mediated keratinocyte necroptosis functions as a self-amplified actor in inflammatory responses and could be considered as an effective therapeutic target. It proposes an innovative prospective that inhibiting keratinocyte necroptosis can prevent the development of epidermal damage in CHS.

Abstract Gasdermin E (GSDME)-mediated pyroptosis is induced in keratinocytes of UVB-challenged skin. The role of GSDME in UVB-caused skin damage remains unknown. To explore the role of GSDME in UVB-induced skin inflammation. We compared differences in skin appearance, histological features, keratinocyte death modalities, infiltration of immune cells, and levels of some inflammatory cytokines between Gsdme −/− mice and wild type (WT) mice after UVB exposure. We explored whether keratinocytes contribute to GSDME deficiency-caused aggravation of UVB-induced skin inflammation in GSDME knockdown keratinocyte cultured in vitro and keratinocyte-specific Gsdme conditional knockout mice. We used anti-Ly6G antibody to deplete neutrophils and explore their role in UVB-caused skin damage. Skin damage and neutrophils infiltration were aggravated in UVB-challenged Gsdme −/− mice, compared with UVB-challenged WT mice. Apoptosis and necroptosis, which were initiated together with GSDME-mediated pyroptosis in UVB-challenged WT mice, were not enhanced in UVB-challenged Gsdme −/− mice. Neutrophils activation indicators and its recruiting cytokines were increased in skin tissue of UVB-challenged Gsdme −/− mice. However, GSDME knockdown did not lead to the further increase of mRNA and secretion of TNF-α and IL-6 in UVB-challenged keratinocytes. Skin damage was not aggravated in UVB-challenged Gsdme cKO mice. Neutrophils depletion alleviated UVB-caused skin damage in WT mice and Gsdme −/− mice, and eliminated its aggravation in Gsdme −/− mice. This study demonstrates that GSDME plays a restrictive role in UVB-induced skin damage through inhibiting excessive recruitment and activation of neutrophils in the immune microenvironment in UVB-caused skin inflammation. However, keratinocytes might not contribute to this restrictive function.

The rostral ventromedial medulla (RVM) is a bulbospinal nuclei in the descending pain modulation system, and directly affects spinal nociceptive transmission through pronociceptive ON cells and antinociceptive OFF cells in this area. The functional status of ON and OFF neurons play a pivotal role in pain chronification. As distinct pain modulative information converges in the RVM and affects ON and OFF cell excitability, neural circuits and transmitters correlated to RVM need to be defined for an in-depth understanding of central-mediated pain sensitivity. In this review, neural circuits including the role of the periaqueductal gray, locus coeruleus, parabrachial complex, hypothalamus, amygdala input to the RVM, and RVM output to the spinal dorsal horn are discussed. Meanwhile, the role of neurotransmitters is concluded, including serotonin, opioids, amino acids, cannabinoids, TRPV1, substance P and cholecystokinin, and their dynamic impact on both ON and OFF cell activities in modulating pain transmission. Via clarifying potential specific receptors of ON and OFF cells, more targeted therapies can be raised to generate pain relief for patients who suffer from chronic pain.

Woodworking manipulators are applied in wood processing to promote automatic levels in the wood industry. However, traditional trajectory planning results in low operational stability and inefficiency. Therefore, we propose a method combining 3-5-3 piecewise polynomial (composed of cubic and quintic polynomials) interpolation and an improved particle swarm optimization (PSO) algorithm to study trajectory planning and time optimization of woodworking manipulators. In trajectory planning, we conducted the kinematics analysis to determine the position information of joints at path points in joint space and used 3-5-3 piecewise polynomial interpolation to fit a point-to-point trajectory and ensure the stability. For trajectory time optimization, we propose an improved PSO that adapts multiple strategies and incorporates a golden sine optimization algorithm (Gold-SA). Therefore, the proposed improved PSO can be called GoldS-PSO. Using benchmark functions, we compared GoldS-PSO to four other types of PSO algorithms and Gold-SA to verify its effectiveness. Then, using GoldS-PSO to optimize the running time of each joint, our results showed that GoldS-PSO was superior to basic PSO and Gold-SA. The shortest running time obtained by using GoldS-PSO was 47.35% shorter than before optimization, 8.99% shorter than the basic PSO, and 6.23% shorter than the Gold-SA, which improved the running efficiency. Under optimal time for GoldS-PSO, our simulation results showed that the displacement and velocity of each joint were continuous and smooth, and the acceleration was stable without sudden changes, proving the method’s feasibility and superiority. This study can serve as the basis for the motion control system of woodworking manipulators and provide reference for agricultural and forestry engineering optimization problems.

The rostral ventromedial medulla (RVM) exerts bidirectional descending modulation of pain attributable to the activity of electrophysiologically identified pronociceptive ON and antinociceptive OFF neurons. Here, we report that GABAergic ON neurons specifically express G protein–coupled estrogen receptor (GPER). GPER+ neurons exhibited characteristic ON-like responses upon peripheral nociceptive stimulation. Optogenetic activation of GPER+ neurons facilitated, but their ablation abrogated, pain. Furthermore, activation of GPER caused depolarization of ON cells, potentiated pain, and ameliorated morphine analgesia through desensitizing μ-type opioid receptor–mediated (MOR-mediated) activation of potassium currents. In contrast, genetic ablation or pharmacological blockade of GPER attenuated pain, enhanced morphine analgesia, and delayed the development of morphine tolerance in diverse preclinical pain models. Our data strongly indicate that GPER is a marker for GABAergic ON cells and illuminate the mechanisms underlying hormonal regulation of pain and analgesia, thus highlighting GPER as a promising target for the treatment of pain and opioid tolerance.

ObjectivesGiven that the histological features of the thyroid parenchyma in patients with Hashimoto's thyroiditis (HT) differ from those of the normal thyroid gland, HT may affect the effectiveness of ultrasound-guided microwave ablation (MWA) for benign thyroid nodules (BTNs). The present study aimed to compare the effectiveness of MWA for the treatment of BTNs in patients with both BTNs and HT and those with BTNs and normal thyroid function, based on changes in the volume reduction ratio (VRR) of the BTNs.MethodsPatients who had achieved a VRR ≥50% after MWA for BTN (July 2020–June 2021), followed up for 12 months, and their data were retrospectively analyzed.ResultsA total of 213 nodules were identified in 185 patients, including 167 in the “BTN” group and 46 in the “BTN + HT” group. A comparison of the fitting curves for VRR–follow-up time revealed that the VRR increased with time after MWA, although the relationship was nonlinear. Piece-wise linear regression model analysis of the threshold effect of VRR and follow-up time in the two groups indicated that the inflection point of the “BTN” group occurred at 2.1 months: VRR increased fastest within 2.1 months of MWA (rate of change: 32.9% per month; P

Objectives To perform a mixed-methods study identifying motivators and deterrents to female doctors interested in core surgical training (CST). To provide tangible implementations based on the findings.Design This study used quantitative (questionnaires) and qualitative (semistructured interviews (SSIs)) analyses. Participants completed online questionnaires on Qualtrics and SSIs were conducted remotely on Microsoft Teams. Questions were derived from previous studies and a novel term, the gender impact rating (GIR), was coined to assess the impact of gender on opportunities available during CST application.Setting Participants were working in the UK National Health Service and data collected from December 2020 to January 2021.Participants A total of 100 female surgical trainees in the UK ranging from Foundation Year 2 to Core Training Year 2.Main outcome measures Participants ranked factors by their influence on their CST application. Of the 100 trainees, 21 were randomly selected for an SSI to explore their questionnaire responses. Statistical analyses were performed using MATLAB and SPSS, alongside a thematic analysis of the interviews.Results A total of 44 out of 100 questionnaire respondents ranked early exposure to surgery as the most influential motivator, while 43% selected work-life balance as the greatest deterrent and 33% suggested mentoring schemes to encourage women to apply to CST. The median GIR was 3 out of 5, indicating a moderate perceived impact of gender on opportunities available during CST application. Qualitative analysis found four overarching themes: institutional factors (including mentorship schemes), organisational culture (including active engagement), social factors and personal factors.Conclusion Thematic analysis suggested that seniors involving women in theatre and a supportive work environment would encourage entry of more female surgeons. Therefore, the proposed implementations are the active engagement of women in theatre and destigmatising less than full-time training. Further research into ethnicity and personality on motivations to enter surgery is advised.

Abstract A recently developed synthetic retinoid abrogates proliferation and induces apoptosis of drug‐resistant malignant‐cancer‐stem‐cell‐like cells. However, the underlying mechanisms of how the synthetic retinoid induces cancer‐stem‐cell‐like cell tumor‐repopulating cell (TRC) apoptosis are elusive. Here, it is shown that although the retinoid and conventional anticancer drugs cisplatin, all‐trans retinoic acid, and tazarotene all inhibit cytoskeletal tension and decondense chromatin prior to inducing TRC apoptosis, half‐maximal inhibitory concentration of the retinoid is 20‐fold lower than those anticancer drugs. The synthetic retinoid induces retinoic acid receptor gamma (RARγ) translocation from the nucleus to the cytoplasm, leading to reduced RARγ binding to Cdc42 promoter and Cdc42 downregulation, which decreases filamentous‐actin (F‐actin) and inhibits cytoskeletal tension. Elevating F‐actin or upregulating histone 3 lysine 9 trimethylation decreases retinoid‐induced DNA damage and apoptosis of TRCs. The combinatorial treatment with a chromatin decondensation molecule and the retinoid inhibits tumor metastasis in mice more effectively than the synthetic retinoid alone. These findings suggest a strategy of lowering cell tension and decondensing chromatin to enhance DNA damage to abrogate metastasis of cancer‐stem‐cell‐like cells with high efficacy.

Butyrophilin Subfamily 3 Member A3 (BTN3A3) is a type I transmembrane protein belonging to the immunoglobulin (Ig) superfamily, which is expressed in many cancers. Clinical data show that ovarian cancer patients with high expression of BTN3A3 have a longer survival time, but the mechanism of BTN3A3 in the occurrence and progression of ovarian cancer is still unclear. Here, we found that BTN3A3 knockdown can promote the proliferation, migration and invasion of ovarian cancer cells, while overexpression of BTN3A3 can inhibit the proliferation, migration and invasion of ovarian cancer cells. We analyzed the immunoprecipitated BTN3A3 complex by mass spectrometry and found that BTN3A3 binds to FGF2, and the overexpression of BTN3A3 leads to a decrease in the protein level of FGF2, which in turn leads to a decrease in the level of phosphorylation of ERK1/2. By increasing the protein level of FGF2, it was found that the level of ERK1/2 phosphorylation also increased. Finally, the cancer promotion phenomenon caused by BTN3A3 knockdown can be improved by using ERK1/2 inhibitor SCH772984. To sum up, BTN3A3 interacts with FGF2, which inhibits FGF2/ERK1/2 axis and ultimately inhibits the proliferation, migration and invasion of ovarian cancer cells. Our results suggest that BTN3A3 may be a prognostic marker and a potential therapeutic target for ovarian cancer.

PurposeGlioma is the most common primary cranial brain tumor that arises from the cancelation of glial cells (which can be in the brain or spinal cord). It is due to innate genetic risk factors or induced by a carcinogenic environment. If left untreated, the disease has a poor prognosis.MethodsIn this study, we downloaded glioma data from TCGA database and GEO (GSE4412). The GSEA database was used to screen tumor microenvironment-related gene sets. Cancer subtypes were classified by GSVA enrichment method.ResultsBy GSVA enrichment analysis, we obtain three Gliomas cancer subtypes. After further survival prognosis analysis and biological function analysis, we obtained 13 tumor microenvironment gene sets and 14 core genes that affect patients’ survival prognosis, and these genes have the potential to become targets for targeted therapies and disease detection.ConclusionWe screened a total of 13 gene sets through a series of enrichment analyses, statistical and prognostic analyses, etc. Among them, 14 core genes were identified, namely: TOP2A, TPX2, BUB1, AURKB, AURKA, CDK1, BUB1B, CCNA2, CCNB2, CDCA8, CDC20, KIF11, KIF20A and KIF2C.

Abstract Background Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. Hypoxia has been found to be one of the factors contributing to chemoresistance in PAC, but also a major driver of the formation of the tumor immunosuppressive microenvironment. However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood. Methods The mRNA expression profiles and corresponding clinicopathological information of PAC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score. Results We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor. Conclusions In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients.

In recent years, physiological signals such as electroencephalograhpy (EEG) have gradually become popular objects of emotion recognition research because they can objectively reflect true emotions.However, the single-modal EEG signal has the problem of incomplete emotional information representation, and the multi-modal physiological signal has the problem of insufficient emotional information interaction.Therefore, a 3D hierarchical convolutional fusion model was proposed, which aimed to fully explore multi-modal interaction relationships and more accurately describe emotional information.The method first extracted the primary emotional representation information of EEG , electro-oculogram (EOG) and electromyography (EMG) by depthwise separable convolution network, and then performed 3D convolution fusion operation on the obtained multi-modal primary emotional representation information to realize the pairwise mode local interactions between states and global interactions among all modalities, so as to obtain multi-modal fusion representations containing emotional characteristics of different physiological signals.The results show that the accuracy in the valence and arousal of the two-class and four-class tasks on DEAP dataset are both 98% by the proposed model.

The microstructure of solution-annealed and aged tensile properties and the stress rupture properties of 15Cr–15Ni titanium-modified austenitic stainless steel with different phosphorus contents were investigated using OM, SEM and TEM. The results showed that two phosphide morphologies were observed after long-term isothermal aging at 850 °C for 1000 h. One was the needle-like M2P distributed within the grain. The other was the blocky M3P distributed at the grain boundaries and twins. The tensile properties of the alloy were unaffected by the phosphorus content, but the stress rupture properties were significantly impacted. With the increase in the phosphorus content from 70 ppm to 250 ppm, the stress rupture life increased from 148 to 269.7 h. Since the strengthening effect of phosphides within the grain or at the grain boundary has been shown to improve the stress rupture properties of alloys, many nanosized granular precipitates, such as the sigma phase, carbides and phosphides, have been observed at the grain boundary, capable of alleviating the stress concentration and limit the crack propagation between two phases, improving the strength of the grain boundary. Intragranular needle-like phosphides can hinder dislocation movements effectively, which improves the intragranular strength of alloys.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. Tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells. Results We found that the expression levels of dendritic cells activated, macrophages M2, and T cells regulatory (Tregs) in ICC were higher than normal tissues, and the expression levels of macrophages M1, monocytes, and T cells follicular helper in ICC were lower than normal tissues. Conclusion These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

Abstract We test the hypothesis that a specific anatomical feature, the dental malocclusion associated with reduced dental wear, causes languages to adapt by relying more heavily on labiodental consonants. In contrast to previous work on this topic, we adopt a usage-based approach that directly examines the relative frequency of such labiodental sounds within phonetically transcribed word lists and texts from thousands of languages. Labiodentals are shown to be very infrequent in the languages of hunter gatherers, who tend to have edge-to-edge bites as opposed to the overbite and overjet observed in populations that consume softer diets and rely heavily on eating utensils. This strong tendency is evident after controlling for Galton’s problem via multiple methods including frequentist and Bayesian linear mixed modeling. Additionally, we discuss data from Amazonian hunter gatherers with edge-to-edge bites. The languages of these populations are shown not to use labiodentals frequently, or to have only recently begun doing so. Finally, we analyze the speech of English speakers with varying bite types, demonstrating how the sounds used by individuals reflect the same phenomenon. The diverse findings converge on the same conclusion: speech adapts to anatomical differences within and across populations.

ObjectiveThis study aimed to construct a radiomics-based MRI sequence from high-resolution magnetic resonance imaging (HRMRI), combined with clinical high-risk factors for non-invasive differentiation of the plaque of symptomatic patients from asyptomatic patients.MethodsA total of 115 patients were retrospectively recruited. HRMRI was performed, and patients were diagnosed with symptomatic plaques (SPs) and asymptomatic plaques (ASPs). Patients were randomly divided into training and test groups in the ratio of 7:3. T2WI was used for segmentation and extraction of the texture features. Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were employed for the optimized model. Radscore was applied to construct a diagnostic model considering the T2WI texture features and patient demography to assess the power in differentiating SPs and ASPs.ResultsSPs and ASPs were seen in 75 and 40 patients, respectively. Thirty texture features were selected by mRMR, and LASSO identified a radscore of 16 radiomics features as being related to plaque vulnerability. The radscore, consisting of eight texture features, showed a better diagnostic performance than clinical information, both in the training (area under the curve [AUC], 0.923 vs. 0.713) and test groups (AUC, 0.989 vs. 0.735). The combination model of texture and clinical information had the best performance in assessing lesion vulnerability in both the training (AUC, 0.926) and test groups (AUC, 0.898).ConclusionThis study demonstrated that HRMRI texture features provide incremental value for carotid atherosclerotic risk assessment.

Light touch can sometimes induce unpleasant itch sensation but the neural correlates of this conversion are not well studied. Here, the authors provide evidence that Tac2 expressing spinal interneurons are connected to gastrin-releasing peptide receptor (GRPR) neurons and form an integral part of the neural circuit underlying touch evoked itch.

Abstract Background Colon adenocarcinoma (COAD) is a gastrointestinal tumor with a high degree of malignancy. Its deterioration process is closely related to the tumor microenvironment, and transcription factors (TF) play a regulatory role in this process. Currently, there is a lack of exploration between the genes related to the COAD tumor microenvironment and the survival prognosis of patients. Models composed of multiple genes usually predict the survival prognosis of patients more accurately than single genes. We can analyze the multigene models that can predict the prognosis of COAD from the current database. Methods The limma package of the R programming language is used for gene differential expression analysis. Kaplan-Meier curve is used to analyze the relationship between the patient risk score model and survival data. The hazard model is used to analyze the relationship between the risk score and the clinical data of COAD patients. The information of immune genes and immune cells is obtained from IMMPORT database and TIMER database. Receiver operating characteristic (ROC) curve is used to judge the stability of the model. Results We found 7 immune genes, which can built a risk score model to predict the survival prognosis of COAD. According to univariate and multivariate analysis, the risk score can be used as an independent predictor. The content of some immune microenvironment cells will also increase as the risk score increases. Conclusions We found 7 immune genes, such as SLC10A2 (solute carrier family 10 member 2), CXCL3 (C-X-C motif chemokine ligand 3), IGHV5-51 (immunoglobulin heavy variable 5-51), INHBA (inhibin subunit beta A), STC1 (stanniocalcin 1), UCN (urocortin), and OXTR (oxytocin receptor), can constitute a model for predicting the prognosis of COAD. They may provide potential therapeutic targets for clinical treatment of COAD.

Austenitic stainless steels are selected as candidate materials for in-core and out-of-core components of Generation-IV fast reactors due to their excellent operating experience in light-water reactors over several decades. However, the performance of conventional austenitic stainless steels proves to be inadequate through operation feedback in fast reactors. To withstand the demands for material performance exposure to the extreme operating environment of fast reactors, modified austenitic stainless steels for in-core and out-of-core components have been developed from the first-generation 300-series steels. The design of an appropriate microstructure becomes a top priority for improving material performance, and key metallurgical features including δ-ferrite content, grain size and secondary phase precipitation pertinent to austenitic stainless steel are focused on in this paper. δ-ferrite content and grain size are closely correlated with the fabrication program and their effects on mechanical properties, especially creep and fatigue properties are critically assessed. Moreover, the impacts of some major elements including nitrogen, stabilization elements (Nb, Ti, V), phosphorus and boron on secondary phase precipitation behaviors during aging or creep are reviewed in detail. Based on the role of the aforementioned metallurgical features, the recommended specification of nitrogen content, stabilization ratio, phosphorus content, boron content, δ-ferrite content and grain size are put forward to guarantee the best-expected performance, which could provide reactors designers with attractive options to optimize fast reactor systems.

Several studies have demonstrated the difficulties in distinguishing malignant lesions of the breast from benign lesions owing to overlapping morphological features on ultrasound. Consequently, we aimed to develop a nomogram based on shear wave elastography (SWE), Angio Planewave Ultrasensitive imaging (Angio PLUS (AP)), and conventional ultrasound imaging biomarkers to predict malignancy in patients with breast lesions. This prospective study included 117 female patients with suspicious lesions of the breast. Features of lesions were extracted from SWE, AP, and conventional ultrasound images. The least absolute shrinkage and selection operator (Lasso) algorithms were used to select breast cancer-related imaging biomarkers, and a nomogram was developed based on six of the 16 imaging biomarkers. This model exhibited good discrimination (area under the receiver operating characteristic curve (AUC): 0.969; 95% confidence interval (CI): 0.928, 0.989) between malignant and benign breast lesions. Moreover, the nomogram also showed demonstrated good calibration and clinical usefulness. In conclusion, our nomogram can be a potentially useful tool for individually-tailored diagnosis of breast tumors in clinical practice.

Hepatocellular carcinoma is a common malignant tumor with poor prognosis, poor treatment effect, and lack of effective biomarkers. In this study, bioinformatics analysis of immune-related genes of hepatocellular carcinoma was used to construct a multi-gene combined marker that can predict the prognosis of patients. The RNA expression data of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and immune-related genes were obtained from the IMMPORT database. Differential analysis was performed by Wilcox test to obtain differentially expressed genes. Univariate Cox regression analysis, lasso regression analysis and multivariate Cox regression analysis were performed to establish a prognostic model of immune genes, a total of 5 genes (HDAC1, BIRC5, SPP1, STC2, NR6A1) were identified to construct the models. The expression levels of 5 genes in HCC tissues were significantly different from those in paracancerous tissues. The Kaplan-Meier survival curve showed that the risk score calculated according to the prognostic model was significantly related to the overall survival (OS) of HCC. The receiver operating characteristic (ROC) curve confirmed that the prognostic model had high accuracy. Independent prognostic analysis was performed to prove that the risk value can be used as an independent prognostic factor. Then, the gene expression data of hepatocellular carcinoma in the ICGC database was used as a validation data set for the verification of the above steps. In addition, we used the CIBERSORT software and TIMER database to conduct immune infiltration research, and the results showed that the five genes of the model and the risk score have a certain correlation with the content of immune cells. Moreover, through Gene Set Enrichment Analysis (GSEA) and the construction of protein interaction networks, we found that the p53-mediated signal transduction pathway is a potentially important signal pathway for hepatocellular carcinoma and is positively regulated by certain genes in the prognostic model. In conclusion, this study provides potential targets for predicting the prognosis and treatment of hepatocellular carcinoma patients, and also provides new ideas about the correlation between immune genes and potential pathways of hepatocellular carcinoma.

In recent years, the information crosstalk between the central nervous system and the periphery has been a hot topic, such as the brain–gut axis, brain–lung axis, etc. Among them, some studies have shown that brainstem nuclei activity can significantly affect the progression of peripheral tumor; however, regarding lung cancer, our understanding of the basic characteristics of the lung-innervating brain nuclei responsive to lung cancer progression remains deficient. Therefore, we used the pseudorabies virus for retrograde labeling of nerves to study the neural circuits between the lung and brain. We then established a mouse orthotopic lung cancer model and used the expression of the c-Fos gene in brain regions to characterize activated brain circuits and compared these results with those of the control group. We focused on c-Fos activity in nuclei associated with retrograde tracing regions of the brainstem. We found over 16 nuclei in the whole brain with direct or indirect lung innervation through neural retrograde labeling with the pseudorabies virus. We further revealed that the neuronal activity of the rostral ventrolateral reticular nucleus (RVL), caudal nucleus of Raphe (raphe obscurus nucleus, ROb), Raphe pallidus nucleus (RPa), and ventral gigantocellular reticular nucleus (GiV) in the rostral ventromedial and lateral medulla were significantly changed in an orthotopic lung cancer mouse model by the immunostaining of c-Fos early responsive protein. Thus, the distinctive rostroventral medulla area, functionally closely related to the vagus nerve, likely plays a role in central neural interaction with peripheral lung tumors and deserves future investigation.

Purpose: We performed a systematic review and meta-analysis of studies that investigated the diagnostic performance of Superb Microvascular Imaging (SMI) in differentiating between benign and malignant breast tumors. Methods: Studies published between January 2010 and March 2022 were retrieved by online literature search conducted in PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Disc, China National Knowledge Infrastructure, Wanfang, and Vip databases. Pooled sensitivity, specificity, and diagnostic odd ratios were calculated using Stata software 15.0. Heterogeneity among the included studies was assessed using I2 statistic and Q test. Meta-regression and subgroup analyses were conducted to investigate potential sources of heterogeneity. Influence analysis was conducted to determine the robustness of the pooled conclusions. Deeks’ funnel plot asymmetry test was performed to assess publication bias. A summary receiver operating characteristic curve (SROC) was constructed. Results: Twenty-three studies involving 2749 breast lesions were included in our meta-analysis. The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.77–0.84, inconsistency index [I2] = 28.32%) and 0.84 (95% CI, 0.79–0.88, I2 = 89.36%), respectively. The pooled diagnostic odds ratio was 19.95 (95% CI, 14.84–26.82). The area under the SROC (AUC) was 0.85 (95% CI, 0.81–0.87). Conclusion: SMI has a relatively high sensitivity, specificity, and accuracy for differentiating between benign and malignant breast lesions. It represents a promising supplementary technique for the diagnosis of breast neoplasms.

BackgroundGastric cancer presents high risk of metastasis and chemotherapy resistance. Hence, it is important to understand the mechanisms of gastric cancer distant metastasis and chemotherapeutic resistance. Our previous study has revealed Four and a Half LIM Domains 3 (FHL3) plays as a binding partner of Glycogen Synthase Kinase 3 Beta (GSK3β), promoted tumor metastasis in pancreatic cancer. However, the role of FHL3 in gastric cancer still remains unclear.MethodsTCGA database and clinical samples are used for exploring the role of FHL3 in disease progression and prognosis. Oxaliplatin (OHP) resistance cell lines were established to study the role of FHL3 in chemotherapy resistance. The experiments about cell proliferation, apoptosis, and metastasis were performed to measure the chemotherapy effects of sh-FHL3 on gastric cancer cell lines and in vivo. That FHL3 changed the EMT phenotype was verified by western blot. Finally, we explored the mechanism of FHL3-mediated EMT and chemotherapy resistance.ResultsmRNA and protein level of FHL3 were significantly up-regulated in gastric cancer tissues when compared with adjacent tissue. FHL3 higher expression is always accompanied with higher TNM stage and worse overall survival. FHL3 over-expressed could lead to OHP resistance. Knockdown of FHL3 slightly inhibited the cell growth, while it obviously sensitized the chemotherapy in vivo and in vitro. In addition, down-regulation of FHL3 increased the mesenchymal markers, such as Slug, Snail, Twist Family BHLH Transcription Factor 1 (Twist1), and Vimentin, while it decreased the epithelial marker E-cadherin. Cell and animal experiments also proved that down-regulation of FHL3 can decrease cancer cell metastasis. For mechanism study, FHL3 knockdown down-regulated the expression level of Mitogen-Activated Protein Kinase (MAPK)/Extracellular Regulated Protein Kinase (ERK) pathway and Transforming Growth Factor-β (TGFβ)/Phosphatidylinositol 3-Kinase (PI3K)/protein kinase B(Akt)/GSK3β-(Ring Finger Protein 146) RNF146/ubiquitin pathway. FHL3 competitively bonded the ubiquitin complex (Slug/GSK3β/RNF146) with Slug and inhibited ubiquitination of Slug. Mesenchymal phenotype cells hold higher level of Multidrug Resistance Gene1 (MDR1), and the FHL3 knockdown reverts the MDR1 in this type cell.ConclusionFHL3 high expression contributed to EMT and chemotherapy resistance via MAPK, and PI3K pathways were activated. FHL3 competitively bonded the ubiquitin complex with Slug, resulting in the up-regulation of Slug and leading to metastasis of gastric cancer.

Abstract Background Enhanced external counterpulsation (EECP) is an effective method for treating patients with cerebral ischemic stroke, while hemodynamics is the major contributing factor in the treatment of EECP. Different counterpulsation modes have the potential to lead to different acute and long-term hemodynamic changes, resulting in different treatment effects. However, various questions about appropriate counterpulsation modes for optimizing hemodynamic effects remain unanswered in clinical treatment. Methods A zero-dimensional/three-dimensional (0D/3D) geometric multiscale model of the cerebral artery was established to obtain acute hemodynamic indicators, including mean arterial pressure (MAP) and cerebral blood flow (CBF), as well as localized hemodynamic details for the cerebral artery, which includes wall shear stress (WSS) and oscillatory shear index (OSI). Counterpulsation was achieved by applying pressure on calf, thigh and buttock modules in the 0D model. Different counterpulsation modes including various pressure amplitudes and pressurization durations were applied to investigate hemodynamic responses, which impact acute and long-term treatment effects. Both vascular collapse and cerebral autoregulation were considered during counterpulsation. Results Variations of pressure amplitude and pressurization duration have different impacts on hemodynamic effects during EECP treatment. There were small differences in the hemodynamics when similar or different pressure amplitudes were applied to calves, thighs and buttocks. When increasing pressure amplitude was applied to the three body parts, MAP and CBF improved slightly. When pressure amplitude exceeded 200 mmHg, hemodynamic indicators almost never changed, demonstrating consistency with clinical data. However, hemodynamic indicators improved significantly with increasing pressurization duration. For pressurization durations of 0.5, 0.6 and 0.7 s, percentage increases for MAP during counterpulsation were 1.5%, 23.5% and 39.0%, for CBF were 1.2%, 23.4% and 41.6% and for time-averaged WSS were 0.2%, 43.5% and 85.0%, respectively. Conclusions When EECP was applied to patients with cerebral ischemic stroke, pressure amplitude applied to the three parts may remain the same. Patients may not gain much more benefit from EECP treatment by excessively increasing pressure amplitude above 200 mmHg. However, during clinical procedures, pressurization duration could be increased to 0.7 s during the cardiac circle to optimize the hemodynamics for possible superior treatment outcomes.

Objective: The prognosis of mild and severe patients has prominent differences during the prevalence of COVID-19, and it will be significant to identify patients' potential risk of progressing to severe cases according to their first clinical presentations. Therefore, we aim to review the clinical symptoms of the COVID-19 epidemic systematically.Methods:We searched PubMed, Embase, Web of Science, and CNKI (Chinese Database) for studies about the clinical features of COVID-19 in China from March 18 to April 18. Then we used REVMAN to conduct a meta-analysis.Results: After screening, 20 articles including 3,326 COVID-19 confirmed cases were selected from 142 articles we retrieved at the beginning of our research. We divided all the cases into a severe group (including severe and critically severe patients) and a mild group according to the “Diagnosis and Treatment Protocol for Novel Coronavirus Infection-Induced Pneumonia” version 4 (trial). Of all the initial symptoms (including fever, cough, abdominal pain, anorexia, chest tightness, diarrhea, dyspnea, expectoration, fatigue, headache, hemoptysis, myalgia, nausea or vomiting, and pharyngalgia) we studied, we found that cough (odds ratio [OR] = 1.4, 95% confidence interval [CI]: 1.2–1.7; p < 0.001), fever (OR = 1.5, 95% CI: 1.2–1.9; p < 0.001), dyspnea (OR = 6.2, 95% CI: 3.6–10.6; p < 0.001), diarrhea (OR = 2.6, 95% CI: 1.3–4.9; p < 0.001), fatigue (OR = 2.1, 95% CI: 1.3–3.3; p < 0.01), expectoration (OR = 1.7, 95% CI: 1.2–2.6; p < 0.01), myalgia (OR = 1.6, 95% CI: 0.8–3.1; p < 0.001), hemoptysis (OR = 4.0, 95% CI: 1.5–11.3; p < 0.001), abdominal pain (OR = 7.5, 95% CI: 2.4–23.4; p < 0.001), and anorexia (OR = 2.8, 95% CI: 1.5–5.1; p < 0.001) had a different distribution in two groups and were statistically significant (p < 0.05).Conclusion:COVID-19 patients whose initial manifestation is dyspnea, hemoptysis, anorexia, diarrhea, or fatigue, especially abdominal pain should be closely monitored to prevent disease deterioration.

Three sustainable development sub-indicators were established along with 49 indicators of sustainable development at the provincial level. We collected data for the key years of 2010, 2015, and 2018 and evaluated the sustainable development level of 31 provinces in China by using the best and worst value improved equal-weight TOPSIS method. With spatial autocorrelation and hotspot analysis, the spatial characteristics of the sustainable development level were studied. Grey correlation analysis and the offset degree index were also used to find out which indicators should be of most concern to improve the level of sustainable development. The results showed the following. (1) The level of sustainable development of China’s provinces is increasing, but there is a decrease from east to west. (2) In terms of sustainable development, the gap between the four major economic regions is narrowing. (3) The overall sustainable development level is highly consistent with the mainstream green development and the human development index, indicating that exploiting the driving force behind developing and improving the quality of development is the key to China’s sustainable development strategy. (4) Different measures should be taken to promote the realization of Sustainable Development Goals in different areas.

BackgroundMetastasis-associated protein 1 (MTA1) has been considered as a transcriptional regulator, which is significantly related to the prognosis in various types of tumors. However, whether MTA1 is a potential prognostic index of gastrointestinal cancer (GIC) remains controversial. The current meta-analysis was performed to evaluate the role of MTA1 expression in the prediction of the clinicopathological features and survival in GIC cases. And the results of gastric cancer were verified by immunohistochemistry (IHC).MethodsEligible studies assessing the relationship between MTA1 and GIC by IHC were searched in the PubMed, Cochrane, Ovid, Web of Science and CNKI databases by various search strategies. The STATA 16.0 software was applied to gather data and to analyze the potential relationship between MTA1 and GIC. The expression level of MTA1 was examined in 80 GC samples by IHC assay. SPSS 20.0 was applied for statistical analysis, and the survival curves were calculated by the Kaplan-Meier method. The data of 95% CI was displayed as “[a-b]”.ResultsAccording to the meta-analysis, the expression level of MTA1 was tightly associated with the tumor size (OR=1.82 [1.16–2.84], P=0.009), tumor tissue differentiation (OR=1.71 [1.24–2.37], P=0.001), depth of invasion (OR=3.12 [2.55–3.83], P

Zinc–ion hybrid supercapacitors are a promising energy storage device as they simultaneously combine the high capacity of batteries and the high power of supercapacitors. However, the practical application of Zinc–ion hybrid supercapacitors is hindered by insufficient energy density and poor rate performance. In this study, a symmetrical zinc–ion hybrid supercapacitor device was constructed with hollow mesoporous-carbon nanospheres as electrode materials, and aqueous ZnSO4 adopted as an electrolyte. Benefiting from the mesoporous structure and high specific area (800 m2/g) of the hollow carbon nanospheres, fast capacitor-type ion adsorption/de-adsorption on both the cathode and the anode can be achieved, as well as additional battery-type Zn/Zn2+ electroplating/stripping on the anode. This device thus demonstrates outstanding electrochemical performance, with high capacity (212.1 F/g at 0.2 A/g), a high energy density (75.4 Wh/kg at 0.16 kW/kg), a good rate performance (34.2 Wh/kg energy density maintained at a high power density of 16.0 kW/kg) and excellent cycling stability with 99.4% capacitance retention after 2,500 cycles at 2 A/g. The engineering of this new configuration provides an extremely safe, high-rate, and durable energy-storage device.

Cancer has always been an enormous threat to human health and survival. Surgery, radiotherapy, and chemotherapy could improve the survival of cancer patients, but most patients with advanced cancer usually have a poor survival or could not afford the high cost of chemotherapy. The emergence of oncolytic viruses provided a new strategy for us to alleviate or even cure malignant tumors. An oncolytic virus can be described as a genetically engineered or naturally existing virus that can selectively replicate in cancer cells and then kill them without damaging the healthy cells. There have been many kinds of oncolytic viruses, such as herpes simplex virus, adenovirus, and Coxsackievirus. Moreover, they have different clinical applications in cancer treatment. This review focused on the clinical application of oncolytic virus and predicted the prospect by analyzing the advantages and disadvantages of oncolytic virotherapy.

Abstract Cronobacter species previously known as Enterobacter sakazakii poses high risks to neonates and infants. In this work a rapid detection method was developed which combined loop-mediated isothermal amplification with lateral flow assay for detection of Cronobacter species in powdered infant formula. The fast amplification reaction without betaine was established and capable of performing DNA replication within 25 min. Based on the novel probe-free labeling methods, we established a lateral flow assay to capture the specific loop-mediated isothermal amplification amplicons which were labeled with fluorescein isothiocyanate and biotin. And the final detection time of this system was within 40 min. The false positive results of the lateral flow assay induced by primer dimer tagged with fluorescein isothiocyanate and biotin were eliminated by Taq single strand DNA binding protein (4 ng/μL). Simultaneously, the efficiency of the fast loop-mediated isothermal amplification assay was achieved. By injection of Taq SSB into the amplification assay as a replacement for betaine, the novel probe-free method could detect Cronobacter species with high specificity and sensitivity at the detection limit in PIF of 101 cfu/g. Our overall strategy has excellent potential in the rapid diagnosis of Cronobacter species label-free by integrating loop-mediated isothermal amplification and lateral flow assay.

Summary: How we sense touch is fundamental for many physiological processes. However, the underlying mechanism and molecular identity for touch sensation are largely unknown. Here, we report on defective gentle-touch behavioral responses in brv1 loss-of-function Drosophila larvae. RNAi and Ca2+ imaging confirmed the involvement of Brv1 in sensing touch and demonstrated that Brv1 mediates the mechanotransduction of class III dendritic arborization neurons. Electrophysiological recordings further revealed that the expression of Brv1 protein in HEK293T cells gives rise to stretch-activated cation channels. Purified Brv1 protein reconstituted into liposomes were found to sense stretch stimuli. In addition, co-expression studies suggested that Brv1 amplifies the response of mechanosensitive ion channel NOMPC (no mechanoreceptor potential C) to touch stimuli. Altogether, these findings demonstrate a molecular entity that mediates the gentle-touch response in Drosophila larvae, providing insights into the molecular mechanisms of touch sensation. : Zhang et al. demonstrate that Brv1 is required for Drosophila larvae to sense gentle touch and mediates the mechanotransduction of class III dendritic arborization neurons. Electrophysiological analysis reveals that Brv1 forms a stretch-activated cation channel. Keywords: touch sensation, mechanosensitive channel, stretch-activated channel, mechanotransduction, Brv1, NOMPC, touch, ion channel

Salmonella typhimurium (S. typhimurium) is a foodborne pathogen that has caused numerous outbreaks worldwide, necessitating the development of on-site strategy to prevent early contamination. Here, we set up an enzyme-free strategy for aptamer-catalyzed hairpin assembly in which salt-induced aggregation of unmodified gold nanoparticles (AuNPs) served as a colorimetric signal output, allowing on-site detection of S. typhimurium in milk. The aptamer-functionalized magnetic beads were used as a vehicle of specifically enriching target bacteria which conjugated with target aptamer to trigger the “Y” shape catalytic hairpin assembly (Y-CHA) circuit. Due to the hairpins desorbing from the surface of AuNPs to the formation of a large amount of double-stranded DNA (dsDNA), AuNPs turned from dispersion to aggregation in the presence of S. typhimurium, resulting in a change of the colorimetric signal from red to blue-gray. The signal output showed a linear relationship for S. typhimurium over a concentration range of 102 to 106 CFU/mL, with a sensitivity of 2.4 × 102 CFU/mL under optimal conditions. The visual protocol has excellent selectivity even in the presence of other competitive bacteria and has been validated in real milk samples with a sensitivity of 2.8 × 103 CFU/mL.

Automotive millimeter-wave (MMW) radar is essential in autonomous vehicles due to its robustness in all weather conditions. Traditional commercial automotive radars are limited by their resolution, which makes the object classification task difficult. Thus, the concept of a new generation of four-dimensional (4D) imaging radar was proposed. It has high azimuth and elevation resolution and contains Doppler information to produce a high-quality point cloud. In this paper, we propose an object classification network named Radar Transformer. The algorithm takes the attention mechanism as the core and adopts the combination of vector attention and scalar attention to make full use of the spatial information, Doppler information, and reflection intensity information of the radar point cloud to realize the deep fusion of local attention features and global attention features. We generated an imaging radar classification dataset and completed manual annotation. The experimental results show that our proposed method achieved an overall classification accuracy of 94.9%, which is more suitable for processing radar point clouds than the popular deep learning frameworks and shows promising performance.