A high hydrophobic moment arginine-rich peptide screened by a machine learning algorithm enhanced ADC antitumor activity.

Cell-penetrating peptides (CPPs) with better biomolecule delivery properties will expand their clinical applications. Using the MLCPP2.0 machine algorithm, we screened multiple candidate sequences with potential cellular uptake ability from the nuclear localization signal/nuclear export signal database and verified them through cell-penetrating fluorescent tracing experiments. A peptide (NCR) derived from the Rev protein of the caprine arthritis-encephalitis virus exhibited efficient cell-penetrating activity, delivering over four times more EGFP than the classical CPP TAT, allowing it to accumulate in lysosomes. Structural and property analysis revealed that a high hydrophobic moment and an appropriate hydrophobic region contribute to the high delivery activity of NCR. Trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, could improve its anti-tumor activity by enhancing targeted delivery efficiency and increasing lysosomal drug delivery. This study designed a new NCR vector to non-covalently bind T-DM1 by fusing domain Z, which can specifically bind to the Fc region of immunoglobulin G and effectively deliver T-DM1 to lysosomes. MTT results showed that the domain Z-NCR vector significantly enhanced the cytotoxicity of T-DM1 against HER2-positive tumor cells while maintaining drug specificity. Our results make a useful attempt to explore the potential application of CPP as a lysosome-targeted delivery tool.

Effects of motivational interviewing intervention on psychological status, compliance behavior and quality of life of patients with malignant tumor combined with diabetes mellitus.

Objective: To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus. Methods: This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared. Results: At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05). Conclusion: Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

Recent progress on nickel phthalocyanine-based electrocatalysts for CO2 reduction.

The electrocatalytic reduction of CO2 to high-value fuels by renewable electricity is a sustainable strategy, which can substitute for fossil fuels and circumvent climate changes induced by elevated CO2 emission levels, making the rational design of versatile electrocatalysts highly desirable. Among all the electrocatalytic materials used in the CO2 reduction reaction, nickel phthalocyanine (NiPc)-based electrocatalysts have attracted considerable attention recently because of their high CO selectivity and catalytic activity. Herein, we review the latest advances in CO2 electroreduction to CO catalyzed by immobilized NiPc and its derivatives on diverse surfaces. Specific strategies, the structure-performance relationship and the CO2-to-CO reaction mechanism of these NiPc-based electrocatalysts are analyzed. Future opportunities and challenges for this series of powerful heterogeneous electrocatalysts are also highlighted.

Modulation of choline and lactate metabolism by basic fibroblast growth factor mitigates neuroinflammation in type 2 diabetes: Insights from 1H-NMR metabolomics analysis.

BACKGROUND: Type 2 diabetes (T2D), a chronic metabolic disease, occurs brain dysfunction accompanied with neuroinflammation and metabolic disorders. The neuroprotective effects of the basic fibroblast growth factor (bFGF) have been well studied. However, the mechanism underlying the anti-inflammatory effects of bFGF remains elusive. METHODS: In this study, db/db mice were employed as an in vivo model, while high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells were used as in vitro models. Liposomal transfection of MyD88 DNA plasmid was used for MyD88-NF-κB pathway studies. And western blotting, flow cytometry and qPCR were employed. 1H-NMR metabolomics was used to find out metabolic changes. RESULTS: bFGF mitigated neuroinflammatory and metabolic disorders by inhibiting cortical inflammatory factor secretion and microglia hyperactivation in the cortex of db/db mice. Also, bFGF was observed to inhibit the MyD88-NF-κB pathway in high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells in in vitro experiments. Moreover, the 1H-NMR metabolomics results showed that discernible disparities between the cortical metabolic profiles of bFGF-treated db/db mice and their untreated counterparts. Notably, excessive lactate and choline deficiency attenuated the anti-inflammatory protective effect of bFGF in SY5Y cells. CONCLUSION: bFGF ameliorates neuroinflammation in db/db mice by inhibiting the MyD88-NF-kB pathway. This finding expands the potential application of bFGF in the treatment of neuroinflammation-related cognitive dysfunction.

High sensitivity of dissolved organic carbon transport during hydrological events in a small subtropical karst catchment.

Dissolved organic carbon (DOC) and discharge are often tightly coupled, though these relationships in karst environments remain poorly constrained. In this study, DOC dynamics over 13 hydrological events, alongside monthly monitoring over an entire hydrological year were monitored in a small karst catchment, SW China. The concurrent analyses of power-law model and hysteresis patterns reveal that DOC behavior is generally transport-limited due to flushing effects of increased discharge but highly variable at both intra- and inter-event scales. The initial discharge at event onset and discharge-weighted mean concentration of DOC ([DOC]DW) of individual events can explain 37.7 % and 19.9 % of the variance of DOC behavior among events, respectively. The sustained dry-cold antecedent conditions make DOC hysteresis behavior during the earliest event complex and different from subsequent events. At event scale, the variability in DOC export is primarily controlled by [DOC]DW (explaining 64.3 %) and the yield of total dissolved solutes (YTDS, explaining 30.4 %), reflecting the impacts of variable hydrological connectivity and intense soil-water-rock interactions in this karst catchment. On an annual scale, DOC yield (YDOC, 222.86 kg C km-2) was mostly derived during the wet season (98.19 %) under the hydrological driving force. The difference in annual YDOC between this karst catchment and other regions can be well explained by annual water yield (Ywater, explaining 24.2 %) and [DOC] (explaining 35.4 %), whereas the variance in DOC export efficiency among catchments is almost exclusively controlled by [DOC] alone, independent of drainage area and annual Ywater. This study highlights the necessity of high-frequency sampling for modeling carbon biogeochemical processes and the particularity of the earliest hydrological events occurred after a long cold-dry period in karst catchments. Under the changing climate, whether DOC dynamics in karst catchments will present source-limited patterns during more extreme hydrological events merits further study.

Multi-role conductive hydrogels for flexible transducers regulated by MOFs for monitoring human activities and electronic skin functions.

Metal organic frameworks (MOFs) have garnered significant attention in the development of stretchable and wearable conductive hydrogels for flexible transducers. However, MOFs used in hydrogel networks have been hampered by low mechanical performance and poor dispersibility in aqueous solutions, which affect the performance of hydrogels, including low toughness, limited self-recovery, short working ranges, low conductivity, and prolonged response-recovery times. To address these shortcomings, a novel approach was adopted in which micelle co-polymerization was used for the ex situ synthesis of Zn-MOF-based hydrogels with exceptional stretchability, robust toughness, anti-fatigue properties, and commendable conductivity. This breakthrough involved the ex situ integration of Zn-MOFs into hydrophobically cross-linked polymer chains. Here the micelles of EHDDAB had two functions, first they uniformly dispersed the Zn-MOFs and secondly they dynamically cross-linked the polymer chains, profoundly influencing the mechanical characteristics of the hydrogels. The non-covalent synergistic interactions introduced by Zn-MOFs endowed the hydrogels with the capacity for high stretchability, high stress, rapid self-recovery, anti-fatigue properties, and conductivity, all achieved without external stimuli. Furthermore, hydrogels based on Zn-MOFs can serve as durable and highly sensitive flexible transducers, adept at detecting diverse mechanical deformations with swift response-recovery times and high gauge factor values. Consequently, these hydrogels can be tailored to function as wearable strain sensors capable of sensing significant human joint movements, such as wrist bending, and motions involving the wrist, fingers, and elbows. Similarly, they excel at monitoring subtle human motions, such as speech pronunciation, distinguishing between different words, as well as detecting swallowing and larynx vibrations during various activities. Beyond these applications, the hydrogels exhibit proficiency in distinguishing and reproducing various written words with reliability. The Zn-MOF-based hydrogels hold promising potential for development in electronic skin, medical monitoring, soft robotics, and flexible touch panels.

Targeted proteomics-determined multi-biomarker profiles developed classifier for prognosis and immunotherapy responses of advanced cervical cancer.

Background: Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity. Methods: Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively. Results: 55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined. Conclusion: Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.

Multiomics integration-based immunological characterizations of adamantinomatous craniopharyngioma in relation to keratinization.

Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

Fungal invasion-induced accumulation of salicylic acid promotes anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple fruits.

In the field, necrosis area induced by pathogens is usually surrounded by a red circle in apple fruits. However, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we demonstrated that accumulated salicylic acid (SA) induced by fungal infection promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module in apple (Malus domestica). Inoculating apple fruits with Valsa mali or Botryosphaeria dothidea induced a red circle surrounding the necrosis area, which mimicked the phenotype observed in the field. The red circle accumulated a high level of anthocyanins, which was positively correlated with SA accumulation stimulated by fungal invasion. Further analysis showed that SA promoted anthocyanin biosynthesis in a dose-dependent manner in both apple calli and fruits. We next demonstrated that MdNPR1, a master regulator of SA signaling, positively regulated anthocyanin biosynthesis in both apple and Arabidopsis. Moreover, MdNPR1 functioned as a co-activator to interact with and enhance the transactivation activity of MdTGA2.2, which could directly bind to the promoters of anthocyanin biosynthetic and regulatory genes to promote their transcription. Suppressing expression of either MdNPR1 or MdTGA2.2 inhibited coloration of apple fruits, while overexpressing either of them significantly promoted fruit coloration. Finally, we revealed that silencing either MdNPR1 or MdTGA2.2 in apple fruits repressed SA-induced fruit coloration. Therefore, our data determined that fungal-induced SA promoted anthocyanin biosynthesis through MdNPR1-MdTGA2.2 module, resulting in a red circle surrounding the necrosis area in apple fruits.

Decoding the Qu-aroma of medium-temperature Daqu starter by volatilomics, aroma recombination, omission studies and sensory analysis.

Qu-aroma is of great significance for evaluation the quality of Daqu starter. This study aimed to decode the Qu-aroma of medium-temperature Daqu (MT-Daqu) via "top-down" and "bottom-up" approaches. Firstly, 52 aroma descriptors were defined to describe the MT-Daqu aroma by quantitative descriptive analysis. Secondly, 193 volatile organic compounds (VOCs) were identified from 42 MT-Daqu samples by HS-SPME-GC-MS, and 43 dominant VOCs were screened out by frequence of occurrence or abundance. By Thin Film (TF)-SPME-GC-O-MS, 27 odors and 90 VOCs were detected in MT-Daqu mixture, and 14 odor-active VOCs were screened out by odor intensity. Thirdly, a five-level MT-Daqu aroma wheel was constructed by matching 52 aroma descriptors and 37 aroma-active VOCs. Finally, Qu-aroma of MT-Daqu was reconstructed with 37 aroma-active VOCs and evaluated by omission experiments. Hereinto, 26 key aroma-active VOCs were determined by OAV value ≥1, including isovaleric acid, 1-hexanol, isovaleraldehyde, 2-octanone, trimethylpyrazine, γ-nonalactone, 4-vinylguaiacol, etc.

Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat.

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Study on energy evolution and fractal characteristics of sandstone with different fracture dip angles under uniaxial compression.

In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress-strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.

Genome-wide association exploratory studies in individuals with ultra-high risk for schizophrenia in Chinese Han nationality in two years follow-up: A subpopulation study.

BACKGROUND: Although ultra-high risk for schizophrenia (UHR) is related to both genetic and environment factors, the precise pathogenesis is still unknow. To date, few studies have explored the Genome-Wide Association Studies (GWAS) in UHR or HR individuals especially in Han population in China. METHODS: In this study, a GWAS analysis for 36 participants with UHR and 43 with HR were performed, and all deletion variations in 22q11 region were also compared. RESULTS: Sixteen individuals with UHR (44.4%) and none with HR converted into schizophrenia in follow-up after two years. Six loci including neurexin-1(NRXN1) (rs1045881), dopamine D1 receptor (DRD1) (rs686, rs4532), chitinase-3-like protein 1 (CHI3L1) (rs4950928), velocardiofacial syndrome (ARVCF) (rs165815), dopamine D2 receptor (DRD2) (rs1076560) were identified higher expression with significant difference in individuals converted into schizophrenia after two years. The Family with Sequence Similarity 230 Member H (FAM230H) gene in the 22q11 region were also found high expression in UHR group. CONCLUSIONS: Further expansion of sample size and validation studies are needed to explore the pathogenesis of these risk loci in UHR conversion into schizophrenia in the future.

Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

Parotid Gland Segmentation Using Purely Transformer-Based U-Shaped Network and Multimodal MRI.

Parotid gland tumors account for approximately 2% to 10% of head and neck tumors. Segmentation of parotid glands and tumors on magnetic resonance images is essential in accurately diagnosing and selecting appropriate surgical plans. However, segmentation of parotid glands is particularly challenging due to their variable shape and low contrast with surrounding structures. Recently, deep learning has developed rapidly, and Transformer-based networks have performed well on many computer vision tasks. However, Transformer-based networks have yet to be well used in parotid gland segmentation tasks. We collected a multi-center multimodal parotid gland MRI dataset and implemented parotid gland segmentation using a purely Transformer-based U-shaped segmentation network. We used both absolute and relative positional encoding to improve parotid gland segmentation and achieved multimodal information fusion without increasing the network computation. In addition, our novel training approach reduces the clinician's labeling workload by nearly half. Our method achieved good segmentation of both parotid glands and tumors. On the test set, our model achieved a Dice-Similarity Coefficient of 86.99%, Pixel Accuracy of 99.19%, Mean Intersection over Union of 81.79%, and Hausdorff Distance of 3.87. The purely Transformer-based U-shaped segmentation network we used outperforms other convolutional neural networks. In addition, our method can effectively fuse the information from multi-center multimodal MRI dataset, thus improving the parotid gland segmentation.

Elevated nitrogen loadings facilitate carbon dioxide emissions from urban inland waters.

Carbon dioxide (CO2) production and emissions from inland waters play considerable roles in global atmospheric CO2 sources, while there are still uncertainties regarding notable nutrient inputs and anthropogenic activities. Urban inland waters, with frequently anthropogenic modifications and severely nitrogen loadings, were hotspots for CO2 emissions. Here, we investigated the spatiotemporal patterns of partial pressure of CO2 (pCO2) and CO2 fluxes (FCO2) in typical urban inland waters in Tianjin, China. Our observation indicated that pCO2 values were oversaturated in highly polluted waters, particularly in sewage rivers and urban rivers, exhibiting approximately 9 times higher than the atmosphere equilibrium concentration during sampling campaigns. Obviously, the spatiotemporal distributions of pCO2 and FCO2 emphasized that the water environmental conditions and anthropogenic activities jointly adjusted primary productivity and biological respiration of inland waters. Meanwhile, statistically positive correlations between pCO2/FCO2 and NH4+-N/NO3--N (p < 0.05) suggested that nitrogen biogeochemical processes, especially the nitrification, played a dominant role in CO2 emissions attributing to the water acidification that stimulated CO2 production and emissions. Except for slight CO2 sinks in waters with low organic contents, the total CO2 emissions from the urban surface waters of Tianjin were remarkable (286.8 Gg yr-1). The results emphasized that the reductions of nitrogen loadings, sewage draining waters, and agricultural pollution could alleviate CO2 emissions from urban inland waters.

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Reliable wafer-scale integration of two-dimensional materials and metal electrodes with van der Waals contacts.

Since the first report on single-layer MoS2 based transistor, rapid progress has been achieved in two-dimensional (2D) material-based atomically thin electronics, providing an alternative approach to solve the bottleneck in silicon device miniaturization. In this scenario, reliable contact between the metal electrodes and the subnanometer-thick 2D materials becomes crucial in determining the device performance. Here, utilizing the quasi-van der Waals (vdW) epitaxy of metals on fluorophlogopite mica, we demonstrate an all-stacking method for the fabrication of 2D devices with high-quality vdW contacts by mechanically transferring pre-deposited metal electrodes. This technique is applicable for complex device integration with sizes up to the wafer scale and is also capable of tuning the electric characteristics of the interfacial junctions by transferring selective metals. Our results provide an efficient, scalable, and low-cost technique for 2D electronics, allowing high-density device integration as well as a handy tool for fundamental research in vdW materials.

Saponin and Ribosome-Inactivating Protein Synergistically Trigger Lysosome-Dependent Apoptosis by Inhibiting Lysophagy: Potential to Become a New Antitumor Strategy.

The susceptibility of lysosomal membranes in tumor cells to cationic amphiphilic drugs (CADs) enables CADs to induce lysosomal membrane permeabilization (LMP) and trigger lysosome-dependent cell death (LDCD), suggesting a potential antitumor therapeutic approach. However, the existence of intrinsic lysosomal damage response mechanisms limits the display of the pharmacological activity of CADs. In this study, we report that low concentrations of QS-21, a saponin with cationic amphiphilicity extracted from Quillaja Saponaria tree, can induce LMP but has nontoxicity to tumor cells. QS-21 and MAP30, a type I ribosome-inactivating protein, synergistically induce apoptosis in tumor cells at low concentrations of both. Mechanistically, QS-21-induced LMP helps MAP30 escape from endosomes or lysosomes and subsequently enter the endoplasmic reticulum, where MAP30 downregulates the expression of autophagy-associated LC3 proteins, thereby inhibiting lysophagy. The inhibition of lysophagy results in the impaired clearance of damaged lysosomes, leading to the leakage of massive lysosomal contents such as cathepsins into the cytoplasm, ultimately triggering LDCD. In summary, our study showed that coadministration of QS-21 and MAP30 amplified the lysosomal disruption and can be a new synergistic LDCD-based antitumor therapy.