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Abstract With global climate change, ecosystems are affected, some of which are more vulnerable than others, such as alpine ecosystems. Microbes play an important role in environmental change in global ecosystems. Plants and microbes are tightly associated, and symbiotic or commensal microorganisms are crucial for plants to respond to stress, particularly for alpine plants. The current study of alpine and subalpine plant microbiome only stays at the community structure scale, but its ecological function and mechanism to help plants to adapt to the harsh environments have not received enough attention. Therefore, it is essential to systematically understand the structure, functions and mechanisms of the microbial community of alpine and subalpine plants, which will be helpful for the conservation of alpine and subalpine plants using synthetic microbial communities in the future. This review mainly summarizes the research progress of the alpine plant microbiome and its mediating mechanism of plant cold adaptation from the following three perspectives: (1) Microbiome community structure and their unique taxa of alpine and subalpine plants; (2) The role of alpine and subalpine plant microbiome in plant adaptation to cold stress; (3) Mechanisms by which the microbiome of alpine and subalpine plants promotes plant adaptation to low-temperature environments. Finally, we also discussed the future application of high-throughput technologies in the development of microbial communities for alpine and subalpine plants. The existing knowledge could improve our understanding of the important role of microbes in plant adaptation to harsh environments. In addition, perspective further studies on microbes’ function confirmation and microbial manipulations in microbiome engineering were also discussed.

Abstract Objective The objective of this research was to create a deep learning network that utilizes multiscale images for the classification of follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) through preoperative US. Methods This retrospective study involved the collection of ultrasound images from 279 patients at two tertiary level hospitals. To address the issue of false positives caused by small nodules, we introduced a multi-rescale fusion network (MRF-Net). Four different deep learning models, namely MobileNet V3, ResNet50, DenseNet121 and MRF-Net, were studied based on the feature information extracted from ultrasound images. The performance of each model was evaluated using various metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, F1 value, receiver operating curve (ROC), area under the curve (AUC), decision curve analysis (DCA), and confusion matrix. Results Out of the total nodules examined, 193 were identified as FTA and 86 were confirmed as FTC. Among the deep learning models evaluated, MRF-Net exhibited the highest accuracy and area under the curve (AUC) with values of 85.3% and 84.8%, respectively. Additionally, MRF-Net demonstrated superior sensitivity and specificity compared to other models. Notably, MRF-Net achieved an impressive F1 value of 83.08%. The curve of DCA revealed that MRF-Net consistently outperformed the other models, yielding higher net benefits across various decision thresholds. Conclusion The utilization of MRF-Net enables more precise discrimination between benign and malignant thyroid follicular tumors utilizing preoperative US.

ABSTRACTSome benign and malignant breast tumours are similar in pathological morphology, which are difficult to be distinguished in clinical diagnosis. In this study, we intended to explore novel biomarkers for differential diagnosis of benign and malignant breast tumours. Methylation EPIC 850K beadchip and RNA-sequencing were used to analyse 29 tissue samples from patients with early-stage breast cancer (BC) and benign breast tumours for differently methylated and expressed genes. The altered methylation of IL21R was semi-quantitatively validated in an independent study with 566 tissue samples (279 BC vs. 287 benign breast tumours) using mass spectrometry. Binary logistic regression analysis was performed to evaluate the association between IL21R methylation and BC. BC-associated IL21R hypomethylation and overexpression were identified in the discovery round. In the validation round, BC patients presented significant IL21R hypomethylation compared to women with benign breast tumours (ORs ≥1.29 per-10% methylation, p-values ≤ 5.69E–14), and this hypomethylation was even enhanced in BC patients with ER-negative and PR-negative tumours as well as with triple-negative tumours. The methylation of IL21R showed efficient discriminatory power to distinguish benign breast tumours from BC (area under curve (AUC) = 0.88), and especially from ER-negative BC (AUC = 0.95), PR-negative BC (AUC = 0.93) and triple-negative BC (AUC = 0.96). We disclosed significant IL21R hypomethylation in patients with BC compared to women with benign breast tumours, and revealed the somatic change of DNA methylation could be a potential biomarker for molecular pathology of BC.

Abstract Liver fibrosis is a major risk factor for hepatocellular carcinoma origin, and its progression not only correlates with oxidative stress and inflammation, but also is encouraged by autophagy hold‐up. Therefore, new solutions to effectively attenuate oxidative stress and inflammation and coincidently favor autophagy are highly demanded to reverse liver fibrosis, and even hamper its escalation into hepatocellular carcinoma. Herein, the porous manganese‐substituted Prussian blue (PMPB) analogs are harnessed to activate autophagy, scavenge reactive oxygen species (ROS), and suppress inflammation for liver fibrosis therapy. PMPB can effectively inhibit macrophage activation, facilitate macrophage autophagy, eradicate ROS, and blockade cellular cross‐talk, thus impeding further inflammation progression. Moreover, the favorable spontaneous capture of PMPB by Kupffer cells allows more PMPB accumulation in liver to significantly attenuate liver injury and collagen deposition, thereby inhibiting the progression of liver fibrosis. PMPB‐based nanomedicine shows great potentials in promoting autophagy activation, eliminating ROS, inhibiting inflammation, and protecting hepatocytes from oxidative stress‐arised damages, which eventually attenuate the extent of liver fibrosis, holding great promise in clinical translation for treating liver fibrosis.

Abstract Background To develop a clinical model for predicting high axillary nodal burden in patients with early breast cancer by integrating ultrasound (US) and clinicopathological features. Methods and materials Patients with breast cancer who underwent preoperative US examination and breast surgery at the Affiliated Hospital of Nantong University (centre 1, n = 250) and at the Affiliated Hospital of Jiangsu University (centre 2, n = 97) between January 2012 and December 2016 and between January 2020 and March 2022, respectively, were deemed eligible for this study (n = 347). According to the number of lymph node (LN) metastasis based on pathology, patients were divided into two groups: limited nodal burden (0–2 metastatic LNs) and heavy nodal burden (≥ 3 metastatic LNs). In addition, US features combined with clinicopathological variables were compared between these two groups. Univariate and multivariate logistic regression analysis were conducted to identify the most valuable variables for predicting ≥ 3 LNs in breast cancer. A nomogram was then developed based on these independent factors. Results Univariate logistic regression analysis revealed that the cortical thickness (p

Abstract To investigate the effect of the antioxidant N-acetylcysteine (NAC) on the proliferation and apoptosis in CG8005 gene-interfering Drosophila S2 embryonic cells by scavenging intracellular reactive oxygen species (ROS). The interfering efficiency of CG8005 gene in Drosophila S2 embryonic cells was verified by real-time quantitative PCR (qRT-PCR). Different concentrations of NAC and phosphate buffered saline (PBS) were used to affect the Drosophila S2 embryonic cells. The growth state of Drosophila S2 embryonic cells was observed by light microscope. Two probes dihydroethidium (DHE) and 2,7-dichlorodihydrofluorescein-acetoacetate (DCFH-DA) were used to observe the ROS production in each group after immunofluorescence staining. TUNEL staining and flow cytometry were used to investigate the apoptosis level of Drosophila S2 embryos, and CCK-8 (Cell Counting Kit-8) was used to detect the cell viability of Drosophila S2 embryos. The knockdown efficiency of siCG8005-2 fragment was high and stable, which was verified by interference efficiency (P

Abstract Objective To investigate the ultrasonographic classification of fetal umbilical-portal-systemic venous shunts (UPSVS) and the correlations with fetal chromosomal abnormalities. Methods We retrospectively analyzed the ultrasound characteristics and the corresponding chromosomal abnormalities of 26 cases of fetal UPSVS prenatally diagnosed. Results A total of 26 fetuses diagnosed as UPSVS were included, including four cases of type I UPSVS, ten of type II, three of type IIIA, and nine of type IIIB. Four cases of type I were all complicated by fetal heart enlargement and heart insufficiency, of which one case had multiple malformations, and all four cases terminated pregnancies. Six of ten cases of type II terminated pregnancies, including four of Down’s syndrome, one of twin reversed arterial perfusion sequence, one of fetal edema but with normal copy number variation (CNV) by chorionic villus sampling. The other four of ten cases were isolated type II with normal chromosomes, which were delivered at full term and were normal in growth and development when followed up 34 months after birth. Three cases of type IIIA all terminated pregnancies, of which one had multiple malformations, one had right multicystic dysplastic kidney, and one had fetal heart enlargement and heart failure. Among nine of type IIIB, seven with chromosomal abnormalities and/ or complicated malformations terminated pregnancies, and two with isolated type IIIB and normal chromosomes were delivered at full term, and were normal in growth and development (one was followed up to 33 months after birth and the other 20 months after birth). Conclusion Fetal UPSVS can be clearly diagnosed and typed by prenatal ultrasonography. Fetal prognosis is determined by the types of UPSVS and complicated malformations and/ or chromosomal abnormalities. The probability of fetal chromosomal abnormalities in UPSVS fetuses is related to the ultrasonographic classification.

Speech emotion recognition is challenging due to the subjectivity and ambiguity of emotion. In recent years, multimodal methods for speech emotion recognition have achieved promising results. However, due to the heterogeneity of data from different modalities, effectively integrating different modal information remains a difficulty and breakthrough point of the research. Moreover, in view of the limitations of feature-level fusion and decision-level fusion methods, capturing fine-grained modal interactions has often been neglected in previous studies. We propose a method named multimodal transformer augmented fusion that uses a hybrid fusion strategy, combing feature-level fusion and model-level fusion methods, to perform fine-grained information interaction within and between modalities. A Model-fusion module composed of three Cross-Transformer Encoders is proposed to generate multimodal emotional representation for modal guidance and information fusion. Specifically, the multimodal features obtained by feature-level fusion and text features are used to enhance speech features. Our proposed method outperforms existing state-of-the-art approaches on the IEMOCAP and MELD dataset.

Abstract The authors present an Ag‐GeTe‐based conductive bridge memory that allows radio frequency (RF) input and transmission. The RF input modifies the resistance switching characteristics and the memory device can switch the order of harmonics of the transmitted RF wave. The transmittance for the RF input above 500 MHz was higher than 0.5 for both the low‐resistance state (LRS) and the high‐resistance state (HRS). Below 500 MHz the transmittance decreased with decreasing frequency and depended on the resistance state (LRS or HRS). At 20 MHz, the transmission for the HRS was 0.02, while that for the LRS was 0.2. An RF input of 20 MHz at 10 dBm modified the SET voltage from 0.19 to 0.05 V, and the RESET voltage from −0.17 to −0.05 V. The RF wave transmitted through the LRS consisted almost entirely of fundamental waves, while that in the HRS provided harmonics or frequency multiplication up to the fifth order at 150 MHz at 10 dBm. Heat cycle measurements with RF input revealed the difference between the non‐linear resistance producing the frequency multiplication and the DC resistance.

Abstract Background The advantages of prophylactic central lymph node dissection (CLND) for clinically node-negative patients remained a great deal of controversies. Our research was aimed to analyze the relationship between cervical central lymph node metastasis (CLNM) and BRAFV600E mutation, ultrasonic and clinicopathologic characterizes in papillary thyroid carcinoma (PTC). Methods and materials In current study, a total of 112 consecutive PTC patients who experienced thyroidectomy plus cervical central neck dissection were included in our research. All PTC were pre-operatively analyzed by ultrasonic features, including tumor size, multifocality or not, tumor location, internal components, echogenicity, microcalcification, margins, orientation, taller than wide shape, and internal vascularity. The presence of clinicopathologic factors, including age, sex, T stage, Hashimoto’s thyroiditis, and BRAFV600E mutation was then investigated. Univariate and multivariate analysis were conducted to check into the relationship between predictive factors and cervical CLNM in PTC patients, and then a predictive model was also established. Results Pathologically, 58.0% (65/112) of the PTC patients harbored cervical CLNM. Univariate and multivariate analysis were conducted to identify age 10 mm, microcalcification, non-concomitant Hashimoto’s thyroiditis and BRAFV600E mutation were predictive factors for cervical CLNM in PTC. The risk score for cervical CLNM in PTC patients was calculated: risk score = 1.284 × (if age 10 mm) + 1.143 × (if microcalcification) – 2.097 × (if concomitant Hashimoto’s thyroiditis) + 1.628 × (if BRAFV600E mutation). Conclusion Age 10 mm, microcalcification, non-concomitant Hashimoto’s thyroiditis and BRAFV600E mutation are predictive factors for cervical CLNM. BRAFV600E mutation by pre-operative US-FNA technology synergized with clinicopathologic and ultrasonic features is expected to guide the appropriate surgical management for PTC patients.

Abstract Background As one typical cardiovascular disease, atherosclerosis severely endanger people’ life and cause burden to people health and mentality. It has been extensively accepted that oxidative stress and inflammation closely correlate with the evolution of atherosclerotic plaques, and they directly participate in all stages of atherosclerosis. Regarding this, anti-oxidation or anti-inflammation drugs were developed to enable anti-oxidative therapy and anti-inflammation therapy against atherosclerosis. However, current drugs failed to meet clinical demands. Methods Nanomedicine and nanotechnology hold great potential in addressing the issue. In this report, we engineered a simvastatin (Sim)-loaded theranostic agent based on porous manganese-substituted prussian blue (PMPB) analogues. The biomimetic PMPB carrier could scavenge ROS and mitigate inflammation in vitro and in vivo. Especially after combining with Sim, the composite Sim@PMPB NC was expected to regulate the processes of atherosclerosis. As well, Mn2+ release from PMPB was expected to enhance MRI. Results The composite Sim@PMPB NC performed the best in regulating the hallmarks of atherosclerosis with above twofold decreases, typically such as oxidative stress, macrophage infiltration, plaque density, LDL internalization, fibrous cap thickness and foam cell birth, etc. Moreover, H2O2-induced Mn2+ release from PMPB NC in atherosclerotic inflammation could enhance MRI for visualizing plaques. Moreover, Sim@PMPB exhibited high biocompatibility according to references and experimental results. Conclusions The biomimetic Sim@PMPB theranostic agent successfully stabilized atherosclerotic plaques and alleviated atherosclerosis, and also localized and magnified atherosclerosis, which enabled the monitoring of H2O2-associated atherosclerosis evolution after treatment. As well, Sim@PMPB was biocompatible, thus holding great potential in clinical translation for treating atherosclerosis. Graphic abstract

Abstract Intratumoral or intestinal microbiota correlates with tumorigenesis and progression, and microbiota regulation for reinforcing various anti‐tumor approaches is of significant importance, which, however, suffers from no precise regulation method and unclear underlying mechanism. Herein, a microbiome metabolism‐engineered phototherapy strategy is established, wherein Nb2C/Au nanocomposite and the corresponding phototherapy are harnessed to realize “chemical” and “physical” bacterial regulations. Flora analysis and mass spectrometry (MS) and metabonomics combined tests demonstrate that the synergistic microbiota regulations can alter the abundance, diversity of intratumoral microbiome, and disrupt metabolic pathways of microbiome and tumor microenvironment, wherein the differential singling pathways and biosynthetic necessities or metabolites that can affect tumor progression are identified. As well, anti‐TNFα is introduced to unite with bacterial regulation to synergistically mitigate bacterial‐induced inflammation, which, along with the metabolism disruptions of intratumoral microbiota and tumor microenvironment, unfreezes tumor resistance and harvests significantly‐intensified phototherapy‐based anti‐tumor outcomes against 4T1 and CT26 tumors. The clear underlying principles of microbiome‐regulated tumorigenesis and the established microbiome metabolism regulation method provide distinctive insights into tumor therapy, and can be also extended to other gut microbiome‐associated lesions interference.

A single-slope greenhouse (SSG) is the general name of a kind of agricultural greenhouse facility widely used in China. Microclimate studies for SSGs in Weifang, Shandong Province, are relatively scarce. This paper mainly discusses the test data of nine SSGs including temperature, humidity, solar global radiation intensity, CO2 concentration, wind speed, and vapor pressure deficit (VPD) trend. Moreover, the conservation of quality method is used to estimate the ventilation volume and humidity growth after opening the top vent in the greenhouse. Through the analysis in this paper, for local SSGs, the internal environmental change has commonality but its internal environment is still influenced by many factors, such as plant planting density, internal cover, plant growth height, and vent opening time. In addition, the method in this paper can provide a quantitative tool for calculating and controlling humidity for researchers and greenhouse workers and provide a basis for greenhouse ventilation strategies.

The shape of conductive filaments in CBRAM is important for resistance switching and conductance modulation, especially in applications like neuromorphic and reservoir computing that use conductance as weight. We report on RF-induced modulation of CBRAM using Ge _2 Sb _3.4 Te _6.2 with sheet-like filaments and compared it to those with dendritic filaments. RF input below 100 MHz reduced SET and RESET voltages, similar to CBRAM with dendritic filaments, but showed significantly different resistance changes. Repeated RF on/off input gradually increased the resistance of low-resistance state, unlike the dendritic filament CBRAM, where the resistance decreased. The increased resistance suggests RF-induced denser sheet-like filaments. Furthermore, the resistance of the high-resistance state showed a peculiar RF-induced resistance change not observed in dendritic filaments. The resistance decreased during RF input and increased to nine times the initial value when RF was switched off. The results show that the conductance modulation by RF input strongly depends on the filament type.

A dimeric Keggin-type phosphotungstate (ODA)10[(PW11FeO39)2O]·9H2O (abbreviated as ODA10[(PW11Fe)2], ODA = octadecyltrimethylammonium bromide) was synthesized and investigated comprehensively its antitumor activity on MCF-7 and A549 cells. The dimeric structure and amorphous morphology were characterized by FT-IR, UV-vis-DRS, SEM and XRD. The in vitro MTT assay of ODA10[(PW11Fe)2] showed anticancer activity on MCF-7 and A549 cells in a dose- and time-dependent manner, and the IC50 values for MCF-7 and A549 cells at 48 h were 5.83 μg/ml and 3.23 μg/ml, respectively. The images of the ODA10[(PW11Fe)2]-treated cells observed by inverted biological microscope exhibited the characteristic morphology of apoptosis. Flow cytometric analysis showed cell apoptosis and cycle arrested at S phase induced by ODA10[(PW11Fe)2]. The above results illuminated the main mechanism of the antitumor action of ODA10[(PW11Fe)2] on MCF-7 and A549 cells, indicating that this dimeric phosphotungstate is a promising anticancer drug.

Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC.

Intellectual disability (ID), one of the most common human developmental disorders, can be caused by genetic mutations in Cullin 4B (Cul4B) and cereblon (CRBN). CRBN is a substrate receptor for the Cul4A/B-DDB1 ubiquitin ligase (CRL4) and can target voltage- and calcium-activated BK channel for ER retention. Here we report that ID-associated CRL4CRBN mutations abolish the interaction of the BK channel with CRL4, and redirect the BK channel to the SCFFbxo7 ubiquitin ligase for proteasomal degradation. Glioma cell lines harbouring CRBN mutations record density-dependent decrease of BK currents, which can be restored by blocking Cullin ubiquitin ligase activity. Importantly, mice with neuron-specific deletion of DDB1 or CRBN express reduced BK protein levels in the brain, and exhibit similar impairment in learning and memory, a deficit that can be partially rescued by activating the BK channel. Our results reveal a competitive targeting of the BK channel by two ubiquitin ligases to achieve exquisite control of its stability, and support changes in neuronal excitability as a common pathogenic mechanism underlying CRL4CRBN-associated ID.