Screening of cancer-specific biomarkers for hepatitis B-related hepatocellular carcinoma based on a proteome microarray.

Hepatocellular carcinoma (HCC) is associated with one of the highest mortality rates among cancers, rendering its early diagnosis clinically invaluable. Serum biomarkers, specifically alpha-fetoprotein (AFP), represent the most promising and widely used diagnostic biomarkers for HCC. However, its detection rate is low in the early stages of HCC progression, and distinguishing specific false positives for other liver-related diseases, such as cirrhosis and acute hepatitis, remains challenging. Therefore, this study was conducted to identify biomarkers for hepatitis B (HBV)-related liver diseases by screening differentially expressed autoantibodies against tumor-associated antigens (TAAbs). We designed a large-scale multistage investigation, encompassing initial screening, HCC-focused, and ELISA validation cohorts to identify potential TAAbs in HBV-related liver diseases, spanning from healthy control (HC) individuals to patients with chronic hepatitis B (CHB), hepatitis B-related cirrhosis (HBC), and HCC, using protein microarray technology. The differential biological characteristics of TAAbs were analyzed using bioinformatics analysis. Validation of tumor-specific biomarkers for HCC was performed using ELISA. In the screening cohort, 547 candidate TAAbs were identified in the HCC group compared to those in the HC group. In the HCC-focused cohort, 64, 61, and 65 candidate TAAbs were identified in the CHB, HBC, and HCC groups, respectively, compared to those in the HC group. Thirty-four proteins exhibited continuously elevated expression from HCs to patients with CHB, HBC, and HCC. Among these, nine were identified as cancer-specific proteins. In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.

Cross-Sectional Study on the Correlation Between Vaginal Microecology and High-Risk Human Papillomavirus Infection: Establishment of a Clinical Prediction Model.

Purpose: High-risk human papillomavirus (HR-HPV) is a significant risk factor for cervical precancerous lesions and cancer. This study aimed to investigate the relationship between vaginal microecology and HR-HPV infection and to evaluate the clinical applicability of vaginal microecology in predicting HR-HPV infection. Patients and Methods: Overall, 2000 women with simultaneously detected vaginal discharge and cervical HPV were selected between March 2022 and March 2023, including 241 and 1759 cases in the HR-HPV positive and HPV negative groups, respectively. Results: No significant differences were found in age, vulvovaginal candidiasis, trichomonas vaginitis, and ß-N-acetylglucosaminosidase between the two groups (P>0.05). Significant differences were observed in Lactobacillus deficiency, bacterial vaginitis (BV), aerobic vaginitis (AV), glucuronidase (GUS), sialidase (SNA), and leukocyte esterase (LE) between the two groups (P<0.05). In the multivariate logistic regression equation, Lactobacillus deficiency, BV, AV, SNA, LE, and GUS were risk factors for HR-HPV infection (P<0.05). Three prediction models, namely, logistic regression, decision tree, and random forest, were established to rank the importance of the predictors. BV ranked first among the three prediction models. The logistic regression model demonstrated the highest accuracy in predicting the risk of HR-HPV infection. The calibration curve of the logistic regression model showed a strong correlation between the predicted and actual probabilities, and decision curve analysis revealed that the prediction model had good clinical applicability. Conclusion: Overall, vaginal microecology imbalance was closely associated with cervical HR-HPV infection, particularly BV and AV. The logistic regression model for the risk of HR-HPV infection based on six predictive factors (BV, AV, LE, SNA, Lactobacillus deficiency, and GUS) had good accuracy and clinical applicability.

Pegylated liposomal doxorubicin in partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer: a prospective study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) for patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer. METHODS: Patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer were recruited in this prospective, open-label, single-arm, multicenter study. Eligible patients were given 4-6 cycles of PLD (40 mg/m2 on day 1, every 4 weeks). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. Exploratory endpoints included the change trend of CA125 and platinum-free interval. RESULTS: Between June 2017 and November 2020, 167 eligible patients were included in the full analysis set. The median PFS and OS were 6.8 months (95% CI, 4.4-9.3 months) and 19.1 months (95% CI, 15.0-23.3 months), respectively. The ORR and DCR were 32.3% and 60.5%, respectively. The ORR (62.3 vs 22.5%) and DCR (84.9 vs 60.7%) of patients with a CA125 decrease after the first cycle were significantly higher than those without a CA125 decrease (all P < .05). Grade ≥ 3 and serious adverse events were reported in 9.9% and 3.9% of patients, respectively. No treatment-related death was observed. CONCLUSION: PLD showed promising efficacy and manageable tolerability in patients with partially platinum-sensitive, platinum-resistant, or platinum-refractory ovarian cancer.ClinicalTrials.gov Identifier: Chinese Clinical Trial Registry, ChiCTR1900022962.

Cation induced changes to the structure of cryptophane cages.

Here the monocation complexes of seven anti-cryptophanes are examined with high-resolution ion-mobility mass spectrometry. The relative size of the [cation + cryptophane]+ complexes were compared based on their measured mobilities and derived collisional cross sections. A paradoxical trend of structural contraction was observed for complexes of increasing cation size. Density functional theory confirmed encapsulation occurs for cation = Na+, K+, Rb+, Cs+ and NH4+. However, cation = Li+ preferred oxygen coordination at a linker over encapsulation within the cavity, leading to a slightly larger gas phase structure overall. Protonated cryptophanes yielded much larger collision cross sections via imploded cryptophane structures. Thus, competing physical effects led to the observed non-periodic size trend of the complexes. Trends in complexation from isothermal titration calorimetry and other condensed phase techniques were borne out by the gas phase studies. Further, predicted cavity sizes compared with the gas phase experimental findings reveal more about the encapsulation mechanisms themselves.

In Situ Closing the van der Waals Gap of Two-Dimensional Materials.

Self-intercalation in two-dimensional (2D) materials, converting 2D materials into ultrathin covalently bonded materials, presents great possibilities for studying a new family of quantum-confined materials with the potential to realize multifunctional behavior. However, understanding the mechanisms and associated in situ kinetics of synthesizing self-intercalated 2D (ic-2D) materials, particularly at the atomic scale, remains elusive, greatly hindering the practical applications of ic-2D crystals. Here, we successfully in situ synthesized ic-2D thin films via thermal annealing of their parental TMDCs inside an electron microscope. We atomically visualized the evolution from TaS2 and NbS2 into the corresponding ic-2D Ta1+xS2 and ic-2D Nb1+xS2, respectively, by in situ scanning transmission electron microscopy (STEM). The self-intercalation process in TaS2 is atomically realized by metal adatom edge adsorption and subsequent diffusion in an atom-by-atom manner. On the other hand, MoS2 and MoSe2 tend to coalesce into metal crystals under the same annealing conditions, suggesting that the self-intercalation process is predominantly controlled by thermodynamic factors as further verified by density functional theory (DFT). By varying the ramping rate and annealing temperature, the coverage and spatial arrangement of the filling sites can be precisely tuned, ranging from 2a × 3a, 3a × 3a, or Ta trimers, as predominantly gauged by kinetic factors. Our work sheds light on the thermodynamics and growth kinetics involved in ic-2D formation and paves the way for growing highly crystalline ic-2D materials with intercalation concentration and topology-dependent properties.

Screening and quantification of pesticides in wetland water, ice, sediment and soil: Occurrence, transport and risk assessment.

Current researches on pesticides in wetlands are limited in terms of screening and quantification of many types of pesticides. Understanding the spatial and temporal dynamics, distribution patterns, and environmental risks of pesticides in multiple media is important for wetland ecological conservation. In this study, 222 pesticides were determined in multimedia samples collected simultaneously from the Songhua Wetland during four seasons. Concentrations of target pesticides in water, ice, sediment and soil ranged from 94.1 to 7445 ng/L, 62.6-953 ng/L, 0.82-50.2 ng/g dw, and 4.32-146 ng/g dw. Large spatial differences (p < 0.05) in pesticide concentrations in ice were found. However, there were no significant differences in the spatial and temporal distribution of pesticides in water, sediment, and soil (p > 0.05), suggesting that there were no correlation between the spatial and temporal use of pesticides. The dynamic exchange of pesticides between water-ice indicated that most pesticides were more enriched in water. However, there were still some pesticides (Dichlorvos and Biphenyl) that showed a stronger tendency to transfer from water to ice. Sediment-water exchange suggested that sediment is a source of secondary releases of most pesticides in wetland ecology, but is a sink for Biphenyl and Oxadiazon. The correlation between concentration ratios and fugacity fraction supported this finding. Most individual pesticides in wetland water and ice had shown low or moderate ecological risk conducted using risk quotient. The cumulative toxic effects of multiple pesticides had a high potential to pose a threat to wetland aquatic organisms.

Protective Effect and Mechanism of L-Theanine on Acute Alcoholic Liver Injury in Mice.

SCOPE: Acute alcoholic liver injury (AALI), a global health concern, is exacerbated by excessive episodic drinking. L-theanine (LTA), a compound found in tea leaves, mitigates the AALI-induced liver oxidative stress and inflammation. However, its relationship with alcohol metabolism and its liver-protective mechanism remains unexplored. METHODS AND RESULTS: This study investigates the protective mechanisms of LTA against AALI in mice. The results demonstrate that LTA mitigates liver tissue damage and reduces the serum levels of aspartate aminotransferase and alanine aminotransferase, and liver levels of triglycerides, malondialdehyde, reactive oxygen species (ROS), tumor necrosis factor-α, interleukin-6, and interleukin-1ß. However, LTA enhances the activity of ethanol-metabolizing enzymes and decreases ethanol and acetaldehyde serum levels. Mechanistically, LTA accelerates alcohol metabolism by upregulating the hepatic expression of ADH6, ALDH1B1, ALDH2, CAT, and ACSS1 mRNA and protein in AALI mice, LTA downregulates the expression of CYP2E1 mRNA and protein and promoting antioxidative activities thus reducing the accumulation of ROS. This attenuated inflammation by inhibiting the phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα) and downregulating the hepatic expression of NF-κB p65, TNF-α, IL-1ß, IL-6 mRNA, and protein. CONCLUSION: LTA is a beneficial dietary supplement that protects against AALI by modulating alcohol metabolism and the TNF-α/NF-κB pathway.

Redefining chimeric antigen receptor T-cell (CAR-T) regulation: China's responses to address secondary cancer risks of CAR-T therapy.

Since the United States Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell (CAR-T) therapy in 2017, it has marked a major breakthrough in cancer treatment, leading to a surge in global research and applications in this field. In recent years, China has made rapid progress, quickly catching up through heavy investment in CAR-T construction, preparation processes, and treatment strategies. China's CAR-T therapy market is driven by substantial pharmaceutical investment targeting its vast population, yet high therapy costs remain uncovered by basic medical insurance. In November 2023, FDA issued a warning about the risk of secondary cancers in patients undergoing CAR-T therapy, sparking global concern. In fact, the China National Medical Products Administration (NMPA) preemptively implemented a series of measures to address the safety concerns of CAR-T therapy, emphasizing the risk of secondary cancers and advising lifelong monitoring as part of the approval process for CAR-T products. Nevertheless, additional regulatory measures are needed to address emerging risks, particularly the threat of secondary cancers. The authors believe that raising the standards for Investigational New Drug (IND) approval and establishing a dynamic reporting and feedback system based on real-world data will strengthen regulatory oversight and support the sustainable growth of the CAR-T industry in China.

Stachyose ameliorates myocardial ischemia-reperfusion injury by inhibiting cardiomyocyte ferroptosis and macrophage pyroptosis.

Myocardial ischemia-reperfusion injury (MIRI) is a complex pathological process that results from the restoration of blood flow to ischemic myocardium, leading to a series of detrimental effects including oxidative stress and inflammation. Stachyose, a naturally occurring oligosaccharide found in traditional Chinese medicinal herbs, has been suggested to possess therapeutic properties against various pathological conditions. However, its impact on MIRI and the underlying mechanisms have not been fully elucidated. In this study, we aimed to investigate the therapeutic effects of stachyose on MIRI and to uncover the molecular mechanisms involved. Using both in vivo and in vitro models of MIRI, we evaluated the effects of stachyose on cardiac function and cell death pathways. Our results indicate that stachyose significantly improves cardiac function and reduces infarct size in MIRI mice. Mechanistically, stachyose modulates the ferroptotic pathway in cardiomyocytes by upregulating the expression of glutathione peroxidase 4 (GPX4) and reducing lipid peroxides and iron levels. Additionally, stachyose inhibits the pyroptotic pathway in macrophages by downregulating the expression of NLRP3, gasdermin D (GSMD-N), and cleaved-caspase-1, leading to decreased levels of proinflammatory cytokines interleukin (IL)-1ß and IL-18. This study demonstrates that stachyose exerts a protective effect against MIRI by targeting both ferroptosis and pyroptosis pathways, suggesting its potential as a novel therapeutic agent for the treatment of MIRI. Further research is warranted to explore the detailed mechanisms and therapeutic potential of stachyose in clinical settings.

Deformable Joule heating electrode based on hybrid layers of silver nanowires and carbon nanotubes and its application in a refreshable multi-cell Braille display.

Stretchable electrodes are an essential component in soft actuator systems. In particular, Joule heating electrodes (JHEs) are required for thermal actuation systems. A highly stretchable, patternable, and low-voltage operating JHE based on hybrid layers of silver nanowires (AgNWs) and carbon nanotubes (CNTs) is reported. The conductive layers were applied on a locally pre-strained bistable electroactive polymer (BSEP) membrane to form a wrinkled conductive surface with a low resistance of 300 Ω/sq, and subsequently patterned to a serpentine trace by laser engraving. The resistance of the resulting electrode remains nearly unchanged up to ~80-90% area strain. By applying a voltage of 7 - 9 V to the electrode, the temperature of the BSEP membrane increased to more than 60 °C, well above the polymer's phase transition temperature of 46 °C, thereby lowering its modulus by a factor of 103. An electronic Braille device based on the JHEs on a BSEP membrane was assembled with a diaphragm chamber. The electrode was patterned into 3 × 2 individually addressable pixels according to the standard U.S. Braille cell format. Through Joule heating of the pixels and local expansion of the BSEP membrane using a small pneumatic pressure, the pixels deformed out of the plane by over 0.5 mm to display specific Braille letters. The Braille content can be refreshed for 20,000 cycles at the same operating voltage.

Efficacy and Safety of Ciprofol Versus Propofol as Anesthetic for Patients Undergoing Painless Colonoscopy.

INTRODUCTION: Ciprofol is a novel propofol analogue with a characteristic of hemodynamic stability. At present, there is a lack of research comparing the hemodynamic stability of ciprofol and propofol during painless colonoscopy. In this study, we aim to test the hypothesis that ciprofol is superior to propofol in terms of hemodynamic stability for sedation anesthesia in patients undergoing colonoscopy. METHODS: A total of 222 patients were randomized into two groups. Patients in group P (n = 112) and group C (n = 110) received propofol and ciprofol sedation, respectively. Noninvasive blood pressure were monitored starting from induction (T0) to the end of the procedure, at 2-min intervals (T1 to T10). Heart rate variability (HRV), pain injection, Modified Observer's Assessment of Alertness and Sedation (MOAA/S) score, body movement, doses of norepinephrine, modified Aldrete score, drug-related adverse reactions, and patient satisfaction and endoscopist satisfaction were recorded. RESULTS: In group C, fewer patients experienced a decrease in blood pressure with a higher HRV after induction sedation, the incidence of pain injection was reduced, the amount of norepinephrine dose was decreased, patient satisfaction was increased compared with group P (all P < 0.05). There were no significant differences in induction time, modified Aldrete score, alertness time, drug-related adverse reactions, and endoscopist satisfaction. CONCLUSIONS: Our study indicated intravenous induction with ciprofol was superior, with regard to hemodynamic stability and reduced injection pain, than induction with propofol for anesthesia in patients undergoing painless colonoscopy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200061814).

Effects of the types and ages of vegetation restoration on land surface roughness in the Eastern Hobq Desert, Northern China.

Vegetation restoration has an important remodelling effect on near-surface characteristics, and consequent changes in land surface roughness (LSR) are key influences on soil wind erosion processes. However, the effects of vegetation restoration types and ages on LSR and the underlying mechanisms are not fully understood. In this study, the sand-fixing vegetation restoration area of the Hobq Desert was examined in comparison to a bare sand control area. The LSR of four artificial vegetation types (Salix psammophila, Caragana korshinskii, Artemisia ordosica, and Populus simonii) with restoration age of 36 years, and Salix psammophila and Caragana korshinskii after different periods of restoration (20, 28, 36 and 45 years) were measured using Structure-from-Motion (SfM) photogrammetry. Near-surface characteristics that may affect LSR were also measured. The results showed that vegetation restoration was associated with a 230-409 % higher LSR compared to the control site (1.74 mm). LSR in the different vegetation restoration areas were ranked, from high to low, as follows: AO (8.85 mm) > CK (7.89 mm) > SP (6.70 mm) > PS (6.61 mm). LSR also increased with time since restoration, with the greatest rate of increase during the first 20 years. The change of LSR is mainly affected by the change of near-surface characteristics, with the direct effects of biological crust thickness (0.331), litter thickness (0.289), soil bulk density (-0.239), and clay content (0.171) being significant. Stem diameter, litter density, biological crust coverage, and soil organic matter affected LSR indirectly, mainly through acting on the above factors. Finally, LSR was effectively estimated based on biological crust thickness, litter thickness, and soil bulk density (R2 = 0.904). The research results will help to further deepen the understanding of the influence mechanism of vegetation restoration on LSR, and provide scientific basis and practical reference for vegetation ecological restoration in similar areas.

Identification of composite ecological corridors and spatial planning guidance in built-up areas under the concept of park city: Taking Shenyang City Center as an example.

The concept of park city provides a new model for the integrated utilization of multiple elements in built-up areas. Ecological corridors, as key components of urban ecosystem, play a major role in facilitating information flow and material exchange between various ecological spaces within built-up area. We identified ecological (mixed) spaces in Shenyang using points of interest data on the ArcGIS 10.2 platform and considered them as sources. Using the least-cost model and gravity model, we identified potential ecological corridors with high, medium, and low resistance on the resistance surface, and proposed the spatial planning guidance strategy based on the distribution characteristics of potential corridors. The results showed that the number of ecological (mixed) spaces in the study area significantly increased during 2017-2022. The ecological resistance surface showed an outward expansion trend with continuous accumulation of resistance in the core area. There was an increase of one high-resistance and one medium-resistance potential corridor, and an increase of nine low-resistance potential corridors. However, there were problems, such as a single corridor network structure, the exacerbation of ecological isolation, and continuous accumulation of resistance. Based on the concept of park city and the spatial distribution characteristics of potential corridors, we put forward a spatial planning guidance strategy to strengthen the support system of composite space corridors.

Artificial intelligence alphafold model for molecular biology and drug discovery: a machine-learning-driven informatics investigation.

AlphaFold model has reshaped biological research. However, vast unstructured data in the entire AlphaFold field requires further analysis to fully understand the current research landscape and guide future exploration. Thus, this scientometric analysis aimed to identify critical research clusters, track emerging trends, and highlight underexplored areas in this field by utilizing machine-learning-driven informatics methods. Quantitative statistical analysis reveals that the AlphaFold field is enjoying an astonishing development trend (Annual Growth Rate = 180.13%) and global collaboration (International Co-authorship = 33.33%). Unsupervised clustering algorithm, time series tracking, and global impact assessment point out that Cluster 3 (Artificial Intelligence-Powered Advancements in AlphaFold for Structural Biology) has the greatest influence (Average Citation = 48.36 ± 184.98). Additionally, regression curve and hotspot burst analysis highlight "structure prediction" (s = 12.40, R2 = 0.9480, p = 0.0051), "artificial intelligence" (s = 5.00, R2 = 0.8096, p = 0.0375), "drug discovery" (s = 1.90, R2 = 0.7987, p = 0.0409), and "molecular dynamics" (s = 2.40, R2 = 0.8000, p = 0.0405) as core hotspots driving the research frontier. More importantly, the Walktrap algorithm further reveals that "structure prediction, artificial intelligence, molecular dynamics" (Relevance Percentage[RP] = 100%, Development Percentage[DP] = 25.0%), "sars-cov-2, covid-19, vaccine design" (RP = 97.8%, DP = 37.5%), and "homology modeling, virtual screening, membrane protein" (RP = 89.9%, DP = 26.1%) are closely intertwined with the AlphaFold model but remain underexplored, which implies a broad exploration space. In conclusion, through the machine-learning-driven informatics methods, this scientometric analysis offers an objective and comprehensive overview of global AlphaFold research, identifying critical research clusters and hotspots while prospectively pointing out underexplored critical areas.

Micro Reference Electrode with an Ultrathin Ionic Path.

Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

Can the digital economy contribute to rural revitalization? A case of from China?

This study establishes a multi-dimensional evaluation index system for measuring digital economy and rural revitalization. It explores the impact of digital economy on China's rural revitalization and its mechanism using dynamic balanced panel data of 30 provinces and cities in China from 2012 to 2020 and adopting two-way fixed effect and mediated effect models. The results reveal that digital economy promotes rural revitalization in China; however, differences exist in its impact on industrial prosperity, ecological livability, civilized rural customs, effective governance, and affluent living under rural revitalization. Heterogeneity analysis shows that the impact of digital economy on rural revitalization is more pronounced in eastern China, with high levels of new urbanization and areas for big-data experimentation. In addition, this thesis verifies that technological innovation and human capital are two important transmission paths through which digital economy affects rural revitalization in China. The conclusions provide theoretical guidance and practical support for China and other developing countries to vigorously develop their digital economies and comprehensively revitalize the countryside.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Objective: Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). Methods: The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. Results: T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. Conclusions: T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

A self-regenerative heat pump based on a dual-functional relaxor ferroelectric polymer.

Electrocaloric (EC) cooling presents a promising approach to efficient and compact solid-state heat pumps. However, reported EC coolers have complex architectures and limited cooling temperature lift. In this work, we introduce a self-regenerative heat pump (SRHP) using a cascade of EC polymer film stacks, which have electrostrictive actuations in response to an electric field that are directed to realize efficient heat transfer, eliminating the need for additional transportive or regenerative mechanisms. The SRHP demonstrates a cooling of 8.8 kelvin below ambient temperature in 30 seconds and delivers a maximum specific cooling power of 1.52 watts per gram. The temperature lift of the SRHP is 14.2 kelvin. These results underscore the potential of the compact solid-state cooling mechanism to address the increasing need for localized thermal management.

First-line treatment with gefitinib in combination with bevacizumab and chemotherapy in advanced non-squamous NSCLC with EGFR-mutation.

BACKGROUND: The safety and efficacy of combination of gefitinib with chemotherapy and bevacizumab in treatment patients with epidermal growth factor receptor (EGFR) mutations are currently unknown. This study was designed to evaluate the safety and preliminary efficacy of a combination therapy consisting of gefitinib, bevacizumab, pemetrexed, and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations. METHODS: Eligible patients with EGFR-mutated advanced non-squamous NSCLC were recruited and received gefitinib combination with bevacizumab plus pemetrexed and carboplatin treatment. The primary endpoints were safety and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS). RESULTS: From June 2019 to June 2021, 20 patients were enrolled in this study. The median follow-up was 33.8 months (95% CI, 31.0-36.6). Grade ≥ 3 adverse events was 65%, including neutropenia (30%), thrombocytopenia (20%), nausea (20%), skin rash (20%), bleeding (10%), and increased ALT (10%). There was no death related to toxicity occurred. The median PFS was 28 months (95% CI, 20.4-35.6). the ORR was 95% (95% CI, 75.1-99.9%), the DCR was 100% (95% CI, 83.2-100%), and the median DOR was 26.4 months (95% CI, 18.9-33.9). The median OS has not been reached. CONCLUSION: The results of this study demonstrate that the four-drug combination regimen, led by gefitinib, is manageable and tolerated and effective for patients with EGFR-mutated advanced non-squamous NSCLC.