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Abstract Global changes and drug abuse are forcing humanity to face various disease problems, and alternative therapies with safe natural substances have important research value. This paper combines various techniques in quantum chemical calculations and molecular simulations to provide molecular-level insight into the dynamics of the self-assembly of N-isopropylacrylamide (NIPAM) for loading curcumin (CUR). The results indicate that increasing the chain length of NIPAM molecules reduces their efficiency in encapsulating and locking CUR, and electrostatic interactions and van der Waals interactions are the main driving forces behind the evolution of system configurations in these processes. The isopropyl groups of NIPAM and the two phenolic ring planes of CUR are the main contact areas for the interaction between the two types of molecules. The thermosensitive effect of NIPAM can alter the distribution of isopropyl groups in NIPAM molecules around CUR. As a result, when the temperature rises from ambient temperature (300 K) to human characteristic temperature (310 K), the NIPAM-CUR interactions and radial distribution functions suggest that body temperature is more suitable for drug release. Our findings offer a vital theoretical foundation and practical guidance for researchers to develop temperature-sensitive drug delivery systems tailored for CUR, addressing its clinical application bottleneck.

Abstract Cancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NADPH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors. Here, using genetically-engineered lung cancer mouse models, we show that G6PD ablation significantly suppresses Kras G12D/+ ;Lkb1 -/- (KL) but not Kras G12D/+ ;P53 -/- (KP) lung tumorigenesis. In vivo isotope tracing and metabolomics reveal that G6PD ablation significantly impairs NADPH generation, redox balance, and de novo lipogenesis in KL but not KP lung tumors. Mechanistically, in KL tumors, G6PD ablation activates p53, suppressing tumor growth. As tumors progress, G6PD-deficient KL tumors increase an alternative NADPH source from serine-driven one carbon metabolism, rendering associated tumor-derived cell lines sensitive to serine/glycine depletion. Thus, oncogenic driver mutations determine lung cancer dependence on G6PD, whose targeting is a potential therapeutic strategy for tumors harboring KRAS and LKB1 co-mutations.

Abstract Giant hepatic cysts may lead to impaired liver function by compressing surrounding tissue, resulting in symptoms such as nausea or portal hypertension. Subharmonic‐aided pressure estimation (SHAPE) offers a noninvasive method for quantitatively estimating pressure and monitoring interstitial fluid pressure. A 55‐year‐old female patient with giant hepatic cysts was admitted to our hospital with elevated protein electrophoretic gamma levels, likely caused by compression of important liver vessels by the cysts. Before surgery, B‐mode ultrasound (BMUS) revealed multiple anechoic cystic lesions with thin, smooth walls in the right lobe. In SHAPE, the curve of the portal vein was lower than that of the hepatic vein, which is absolutely different from a healthy volunteer in our previous SHAPE study. It suggested that the patient may have had portal hypertension. Three days after laparoscopic fenestration and drainage of hepatic cysts, the size of the largest cyst had decreased on BMUS and protein electrophoretic gamma levels had normalized. While the curve of the portal vein remained lower than that of the hepatic vein, the difference between them had decreased compared to presurgery levels. SHAPE shows promise as a tool for noninvasively estimating portal hypertension and improving prognosis assessment in patients.

Late blight caused by Phytophthora infestans is the most devastating disease of potato. Phytophthora infestans produces many secondary metabolites and effector proteins, involved in the pathogenesis, which compromise host defense mechanisms. Pectinesterase (PE) is a cell wall degrading enzyme secreted by P. infestans to infect the host. To examine the role of PE in P. infestans, 15 strains of P. infestans were isolated from infected potato leaves in Yunnan, China. We analyzed the biological effects of exogenously added PE on P. infestans and its activity and gene expression after infection of potato using quantitative real-time polymerase chain reaction (RT-PCR). It was found that PE significantly promotes the growth of P. infestans, increases the weight of mycelium and the number of sporangia, and promotes the sporangial germination. PE accelerated the infection process of P. infestans on potato. The pathogenicity of P. infestans was positively correlated with PE activity and gene expression. PE is a key to the virulence difference of potato late blight.

BackgroundObesity is becoming more widely acknowledged as a chronic illness that raises the risk of oncogenesis. This inquiry aimed to look into the correlation between cancer patient mortality and obesity, as measured by the weight-adjusted waist index (WWI).MethodsWe used continuous data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 as the benchmark, with a follow-up validity period of December 31, 2019. First, we assessed the correlation between WWI and the all-cause and cause-specific execution of cancer sufferers using multivariable Cox proportional hazards models. Second, a smoothed curve fit was utilized to examine the relationship between WWI and both cause-specific and all-cause mortality in cancer patients. Lastly, we analyzed the relationship between WWI and both cause-specific and all-cause mortality in cancer patients, to find out if this link held across the population subgroup evaluation and impact analyses were used as well during the last step.ResultsWith a median follow-up of 87.8 months, 1,547 (34.7%) of the 4,463 cancer patients had deceased. Among them, 508 (11.4%) succumbed to cancer, while 322 (7.2%) passed away due to cardiovascular disease. Multivariate Cox proportional hazards model of mortality among cancer patients revealed an all-cause mortality hazard ratio [HR=1.13; 95% CI (1.04, 1.23)] and cardiovascular mortality [HR=1.39; 95% CI (1.16, 1.67)]. Furthermore, for each unit increase in WWI, all-cause mortality was significantly higher in male cancer survivors than in female cancer survivors.ConclusionsOur study reveals substantial correlations between WWI and all-cause and cardiovascular mortality in US cancer survivors, helping to identify cancer survivors at higher risk of death and thus potentially guiding targeted interventions.

This study focuses on the problem of ‘teachers’ teaching’ and ‘students’ learning’ in college education courses. It aims to introduce the Deep Learning theory into the teaching of ideological and political theory courses in universities; deepen the theoretical framework of education courses and the associated learning, maintenance, promotion, and support mechanisms; and realise the modernisation of teaching ideas and strategies. A quantitative and qualitative questionnaire survey was used to analyse respondents’ learning experience and effect. Most participants had a significant learning experience and effect under the DL mechanism, a large sense of gain, and a strong cognition and acceptance of IPTCs. We also found positive correlations between whether participants chose political subjects and their learning motivation and interest, between classroom attention and overall sense of gain, and between learning interest and overall sense of gain. The results can inform teaching innovations, optimise teaching strategies, and improve the teaching effect of IPTCs in the digital education era.

Visual Dialog is a multi-modal task involving both computer vision and dialog systems. The goal is to answer multiple questions in conversation style, given an image as the context. Neural networks with attention modules are widely used for this task, because of their effectiveness in reasoning the relevance between the texts and images. In this work, we study how to further improve the quality of such reasoning, which is an open challenge. Our baseline is the Recursive Visual Attention (RVA) model, which refines the vision-text attention by iteratively visiting the dialog history. Building on top of that, we propose to improve the attention mechanism with contrastive learning. We train a Matching-Aware Attention Kernel (MAAK) by aligning the deep feature embeddings of an image and its caption, to provide better attention scores. Experiments show consistent improvements from MAAK. In addition, we study the effect of using Multimodal Compact Bilinear (MCB) pooling as a three-way feature fusion for the visual, textual and dialog history embeddings. We analyze the performance of both methods in the discussion section, and propose further ideas to resolve current limitations.

The handheld ultrasound has been widely applied in various clinical applications due to its high portability and cost-effectiveness advantages. The smaller hardware architecture can expand its range of application scenarios. However, miniaturized ultrasound devices face the challenges in terms of image quality, frame rate, and power consumption. The achievement of high-quality and high-frame-rate imaging depends on numerous channels and higher pulse repetition frequency (PRF) at the cost of power consumption. The proposed work aims to design a field-programmable gate array (FPGA)-based prototype with synthetic aperture method for portable and cost-effective handheld ultrasound system. The prototype supports 8 transmit and receive channels and forms up to 8 synthetic apertures. In addition, to optimize the FPGA resources, the auto delay calculation and segmented apodizations are employed for 4 parallel beamforming lines. To evaluate the performance of our proposed prototype, scan sequences of B-mode, C-mode, and D-mode are implemented for image construction. The results show that the proposed prototype can provide a lateral resolution of 0.30 mm, a contrast-to-noise ratio (CNR) of 7.58 dB, and a frame rate of 22 frames per second (FPS) in dual-mode imaging. Moreover, it is remarkable that the memory and logic resources in the FPGA (EP4CE55) account for 73.7% and 66.2%, respectively, which makes the FPGA's power consumption only about 530 mW. The proposed prototype is suitable for handheld and other miniaturized ultrasound imaging systems.

Cancer subtyping (or cancer subtypes identification) based on multi-omics data has played an important role in advancing diagnosis, prognosis and treatment, which triggers the development of advanced multi-view clustering algorithms. However, the high-dimension and heterogeneity of multi-omics data make great effects on the performance of these methods. In this paper, we propose to learn the informative latent representation based on autoencoder (AE) to naturally capture nonlinear omic features in lower dimensions, which is helpful for identifying the similarity of patients. Moreover, to take advantage of survival information or clinical information, a multi-omic survival analysis approach is embedded when integrating the similarity graph of heterogeneous data at the multi-omics level. Then, the clustering method is performed on the integrated similarity to generate subtype groups. In the experimental part, the effectiveness of the proposed framework is confirmed by evaluating five different multi-omics datasets, taken from The Cancer Genome Atlas. The results show that AE-assisted multi-omics clustering method can identify clinically significant cancer subtypes.

The current study presents a comprehensive investigation on the precipitation reaction and supramolecular interactions between berberine hydrochloride (BBR) and baicalin (BA) in an aqueous system. Utilizing a combination of multi-spectral analytical techniques and molecular dynamic simulations, we elucidated the mechanism of the complexion process. The precipitate formation was observed within a drug concentration range of 0.1–1.0 mM, and a 1:1 stoichiometry ratio of BBR to BA was established by the Job's plot method. Morphological and structural characterizations of the precipitates were conducted using DSC, FTIR and PXRD. Additionally, UV–Vis absorption and 1H NMR spectroscopy were employed to compare the spectral characteristics of the precipitates with those of individual drug solution. Molecular dynamic simulations further dissected the intermolecular interactions and self-assembly mechanisms. The precipitates formed were amorphous microparticles with an average diameter of approximately 20 μm, primarily stabilized by hydrogen bonding and π–π stacking. This study contributes foundational insights into the supramolecular interactions between BBR and BA, therefore facilitated a better understanding of the precipitation process involving flavonoid-alkaloid pairs in mixed aqueous solutions.

Background: Primary hepatic lymphoepithelioma-like carcinoma (LELC) is a malignant tumor with a low incidence, but the number of case reports has increased in recent years. The prognosis of hepatic LELC is better than hepatocellular carcinoma (HCC). The differentiation between hepatic LELC and HCC has clinical value during follow-up treatment. The purpose of our study was to compare contrast-enhanced ultrasound (CEUS) imaging features in patients with hepatic LELC and HCC. Methods: Twelve patients with an average age of 60.1±9.5 years and histopathologically confirmed hepatic LELC were included in the study. Forty-three patients with an average age of 57.4±9.0 years and a histopathological diagnosis of HCC were designated as the control group by means of propensity score matching (1:4). The clinical data, B-mode ultrasound (BMUS), and CEUS features were retrospectively analyzed between patients with hepatic LELC and HCC. Results: The serum a-fetoprotein (58.1% [25/43] vs.16.7% [2/12]; p=0.017) and des-gamma-carboxy prothrombin levels (74.4% [32/43] vs.16.7% [2/12]; p=0.001) were not significantly elevated in patients with hepatic LELCs compared to HCCs. LELCs were mainly hypoechoic based on BMUS, while the echogenicity of HCCs varied (p=0.016). A halo sign was less common in patients with hepatic LELCs than HCCs (16.7% [2/12] vs. 58.1% [25/43]; p=0.011). Of hepatic LELCs, 75% (9/12) had homogeneous hyperenhancement based on CEUS, whereas 58.1% (25/43) of HCCs had heterogeneous hyperenhancement (p=0.004). Early washout was noted in 91.7% (11/12) of hepatic LELCs compared to 46.5% (20/43) of HCCs (p=0.005). Furthermore, hepatic LELCs were more likely to exhibit peripheral rim-like hyperenhancement (83.3% [10/12] vs. 11.6% [5/43]; p < 0.001). Conclusion: BMUS and CEUS are helpful in discriminating between hepatic LELC and HCC. A hypoechoic mass, the rare halo sign, homogeneous hyperenhancement in the arterial phase, higher frequencies of early washout, and peripheral rim-like hyperenhancement are useful ultrasound features that can help differentiate hepatic LELCs from HCCs.

Soil salinity is a major abiotic stress limiting crop production globally. Oat (Avena sativa) is an annual cereal with a strong salt tolerance, a high yield, and nutritional quality, although the mechanisms underlying its salt stress response remain largely unknown. We examined the physiological and transcriptomic responses of A. sativa seedlings to salt stress in tolerant cultivar Qingyongjiu 195 and sensitive cultivar 709. Under salt stress, Qingyongjiu 195 maintained a higher photosynthetic efficiency, antioxidant enzymes activity, and leaf K+ accumulation but a lower Na+ uptake than 709. RNA-seq revealed 6616 differentially expressed genes (DEGs), including 4265 up- and 2351 downregulated. These were enriched in pathways like plant–pathogen interaction, phenylpropanoid biosynthesis, and MAPK signaling. We specifically highlight DEGs involved in photosynthesis (chlG, CP47 psbB, COX2, LHCB) and antioxidants (trxA, GroES). Qingyongjiu 195 also appeared to enhance K+ uptake via KAT1 and AKT2 and sequester Na+ in vacuoles via NHX2. Additionally, HKT restricted Na+ while promoting K+ transport to shoots, maintaining K+/Na+. The expression levels of CAX, ACA, CML, CaM, and CDPK in Qingyongjiu 195 were higher than those in 709. Oats regulated Ca2+ concentration through CAX and ACA after salt stress, decoded Ca2+ signals through CML, and then transferred Ca2+ signals to downstream receptors through the Ca2+ sensors CaM and CDPK, thereby activating K+/Na+ transporters, such as SOS1 and NHX, etc. Our results shed light on plant salt stress response mechanisms and provide transcriptomic resources for molecular breeding in improving salt tolerance in oats.

An experiment was conducted on a prestressed concrete (PC) composite girder bridge with steel truss webs to investigate its flexural performance. The mechanical characteristics and failure modes of a PC composite girder bridge with steel truss webs was clarified. Finite element (FE) analysis was carried out, and the influence of the girder height-to-span ratio and eccentric loading effect on the flexural performance of a composite beam bridge with a steel truss web was discussed. The method for calculating the cracking bending moment, the bending moment at the rebar yield stage, and the ultimate bending moment of a PC composite girder with steel truss webs was proposed. Key findings include that, in both the elastic and cracking elastic stages, the strain of the bottom and top conforms to the plane-section assumption. Throughout the loading process, there was no occurrence of joint failure or local buckling failure in the steel truss webs; the composite girder ultimately fails due to excessive deformation, indicating that the overall mechanical performance of the composite beam is good. The deflection and stress in the mid-span section decrease with an increasing height-to-span ratio, and there are significant impacts of eccentric loading on deflection and stress. Compared with the results of the FE analysis and test, the calculation methods of the cracking moment, reinforcement yield moment, and ultimate moment of PC composite girders with steel truss webs presented in this paper have a high accuracy.

Using black bean, soybean and soybean meal as raw materials, soy sauce was prepared by high-salt dilution method. The quality indexes, functional components and antioxidant activities of the three soy sauce were detected by conventional methods and liquid chromatography-mass spectrometry (LC-MS/MS), and the correlation between antioxidant activities and functional components was analyzed. Partial least squares discriminant analysis (PLS-DA) was performed based on the functional components of soy sauce. The results showed that the sensory and physicochemical indexes of the three kinds of soy sauce all met the requirements of the first grade soy sauce in national standard GB 18186-2000 "Brewing Soy Sauce". The functional components of the three kinds of soy sauce (total phenols, total flavonoids, melanoid, total free polyphenols, total free flavonoids, total free amino acids) were 4.78~7.14 mgGAE/mL, 2.75~4.34 mgRE/mL, 1.25%~1.70%, 25.54~35.08 μg/mL, 11.37~20.20 μg/mL, 42.36~48.61 mg/mL, respectively. The antioxidant indexes (total antioxidant capacity, ABTS+ and DPPH free radical scavenging rate) were 24.27~605.57 U/mL, 6.43~8.57 mgVCE/mL and 3.53~5.30 mgVCE/mL, respectively. Except for free amino acids, the functional components contents and antioxidant activities of the three kinds of soy sauce were black soy sauce>soybean meal soy sauce>soybean soy sauce, and there were significant differences in antioxidant indexes among the three soy sauce (P

This study evaluates the characteristics of river runoff and sediment changes in the Wei River mainstream over the past 50 years based on runoff and sediment data and meteorological data from 1971 to 2020 at the Huaxian hydrological station in the lower reaches of the Wei River. The main research methods are the Mann–Kendall method, wavelet analysis, cross-wavelet analysis, and cumulative curve method. The results show that there is no significant decreasing trend and abrupt change in runoff volume in recent years, the decreasing trend of sediment transport is obvious, and the abrupt change occurs around 2006. The dominant periodicity of runoff is 12–13a, and the dominant periodicity of sediment transport is 5a. There is only a significant resonance periodicity of 3–5a in 1980–1990, which is roughly a positive correlation. The runoff–sediment series can be divided into four time periods, and the reasons for the change in the runoff–sediment relationship are different in each time period. The precipitation factor has a slightly greater impact on runoff and a weak impact on sediment transport, with contribution rates of 21.2 and 7.6%. Human activities such as subsurface changes and water conservancy construction have a greater impact on runoff and sediment load, with contribution rates of 78.8 and 92.4%. HIGHLIGHTS In this study, the resonance period between water and sediment is deeply studied by cross-wavelet analysis, and the mutual influence law between water and sediment in the mainstream of Weihe River is revealed.; This study quantitatively assessed the impacts of climate change and human activities on runoff and sediment transport and analyzed the impact process in detail.;

Lung cancer is responsible for the highest number of cancer-related deaths, with non-small cell lung cancer (NSCLC) being the most prevalent subtype. A critical aspect of managing lung cancer is reducing morbidity and mortality rates among NSCLC patients. Identifying high-risk factors for lung cancer and facilitating early diagnosis are invaluable in achieving this objective. Recent research has highlighted the association between insulin resistance and the development of NSCLC, further emphasizing its significance in the context of lung cancer. It has been discovered that improving insulin resistance can potentially inhibit the progression of lung cancer. Consequently, this paper aims to delve into the occurrence of insulin resistance, the mechanisms underlying its involvement in lung cancer development, as well as its potential value in predicting, assessing, and treating lung cancer.

Summary: The many exotic properties of carbon nanotubes (CNTs) make them a powerful attraction in the field of drug delivery systems (DDS). In this work, based on quantum chemical calculation and molecular simulation techniques, polyacrylic acid (PAA) and N-isopropyl acrylamide (NIP) are selected and acted simultaneously on the CNT to form a stable system (FCNT). As a potential DDS, FCNT captures the dispersed doxorubicin (DOX) molecules around it and maintains a stable configuration. In these processes, electrostatic and van der Waals forces act synergistically, with van der Waals forces dominating. Compared to NIP, PAA molecules exhibit stronger adhesion and encapsulation efficiency to CNT and stronger adsorption capacity to DOX. This study reveals the mechanism of action among PAA, NIP, CNT, and DOX, providing feasibility verification and prospective guidance for the experimental synthesis of PAA-NIP-CNT-type multifunctional DDS, and also broadening the idea for exploring more efficient DDS suitable for DOX.

PurposeIn chronic thromboembolic pulmonary hypertension (CTEPH), fibrosis of thrombi in the lumen of blood vessels and obstruction of blood vessels are important factors in the progression of the disease. Therefore, it is important to explore the key genes that lead to chronic thrombosis in order to understand the development of CTEPH, and at the same time, it is beneficial to provide new directions for early identification, disease prevention, clinical diagnosis and treatment, and development of novel therapeutic agents.MethodsThe GSE130391 dataset was downloaded from the Gene Expression Omnibus (GEO) public database, which includes the full gene expression profiles of patients with CTEPH and Idiopathic Pulmonary Arterial Hypertension (IPAH). Differentially Expressed Genes (DEGs) of CTEPH and IPAH were screened, and then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analyses were performed on the DEGs; Weighted Gene Co-Expression Network Analysis (WGCNA) to screen the key gene modules and take the intersection genes of DEGs and the key module genes in WGCNA; STRING database was used to construct the protein-protein interaction (PPI) network; and cytoHubba analysis was performed to identify the hub genes.ResultsA total of 924 DEGs were screened, and the MEturquoise module with the strongest correlation was selected to take the intersection with DEGs A total of 757 intersecting genes were screened. The top ten hub genes were analyzed by cytoHubba: IL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4.ConclusionIL-1B, CXCL8, CCL22, CCL5, CCL20, TNF, IL-12B, JUN, EP300, and CCL4 have diagnostic and therapeutic value in CTEPH disease, especially playing a role in chronic thrombosis. The discovery of NF-κB, AP-1 transcription factors, and TNF signaling pathway through pivotal genes may be involved in the disease progression process.

AbstractObjective To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients.Methods This retrospective study recruited 57 patients aged 20–40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023.Results During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46–6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed.Conclusion FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

Abstract LKB1 and KRAS are the third most frequent co-mutations detected in non-small cell lung cancer (NSCLC) and cause aggressive tumor growth. Unfortunately, treatment with RAS-RAF-MEK-ERK pathway inhibitors has minimal therapeutic efficacy in LKB1-mutant KRAS-driven NSCLC. Autophagy, an intracellular nutrient scavenging pathway, compensates for Lkb1 loss to support Kras-driven lung tumor growth. Here we preclinically evaluate the possibility of autophagy inhibition together with MEK inhibition as a treatment for Kras-driven lung tumors. We found that the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and the MEK inhibitor Trametinib displays synergistic anti-proliferative activity in Kras G12D/+; Lkb1 -/- (KL) lung cancer cells, but not in Kras G12D/+; p53 -/- (KP) lung cancer cells. In vivo studies using tumor allografts, genetically engineered mouse models (GEMMs) and patient-derived xenografts (PDXs) showed anti-tumor activity of the combination of HCQ and Trametinib on KL but not KP tumors. We further found that the combination treatment significantly reduced mitochondrial membrane potential, basal respiration, and ATP production, while also increasing lipid peroxidation, indicative of ferroptosis, in KL tumor-derived cell lines (TDCLs) and KL tumors compared to treatment with single agents. Moreover, the reduced tumor growth by the combination treatment was rescued by ferroptosis inhibitor. Taken together, we demonstrate that autophagy upregulation in KL tumors causes resistance to Trametinib by inhibiting ferroptosis. Therefore, a combination of autophagy and MEK inhibition could be a novel therapeutic strategy to specifically treat NSCLC bearing co-mutations of LKB1 and KRAS.

Abstract Background In this study, the changes of vaginal microbiome after focused ultrasound (FU) treatment were evaluated to explore the possible mechanism of FU in the treatment of high-risk human papillomavirus (HR-HPV) infection. Methods This study was nested in the FU arm of a prospective cohort study. A total of 37 patients diagnosed with HR-HPV infection-related cervical low-grade squamous intraepithelial lesion (LSIL) who met the inclusion criteria were enrolled in this study from October 2020 to November 2021, and these patients were treated with FU. We used 16S ribosomal RNA (16S rRNA) gene amplicon sequencing to profile the vaginal microbiota composition of patients before and 3 months after FU treatment. Results After FU treatment, HR-HPV was cleared in 24 patients, with a clearance rate of 75.0% (24/32). Lactobacillus iners was the predominant species among all samples. No significant difference was found in alpha-diversity index before and 3 months after FU treatment (P > 0.05), but the rarefaction curves showed that the vaginal microbial diversity before FU treatment was higher than that after FU treatment. Linear discriminant analysis (LDA) effect size (LEfSe) showed that Bifidobacterium contributed the most to the difference between the two groups at the genus level, and the abundance after FU treatment was significantly higher than that before treatment (P = 0.000). Conclusions The decrease of vaginal microbial diversity may be related to the clearance of HR-HPV infection, and FU treatment contributed to the decrease of vaginal microbial diversity. Increased Bifidobacterium abundance in the vaginal microbiome may be associated with clearance of HR-HPV infection, and FU treatment may contribute to the increase in Bifidobacterium abundance. Trial registration number: This study was registered in the Chinese Clinical Trial Registry on 23/11/2020 (ChiCTR2000040162).

Objectives To assess the efficacy and safety of focused ultrasound (FU) for high-risk human papillomavirus (HR-HPV) infection-related cervical low-grade squamous intraepithelial lesions (LSIL).Methods Of 185 patients who met the inclusion criteria for this prospective study from October 2020 to November 2021, 95 received FU and 90 were followed up only. At the six-month follow-up, the HR-HPV clearance and LSIL regression rates of the groups were compared and factors affecting HR-HPV clearance were analyzed. The safety and side effects of FU were evaluated.Results No significant difference was found in the baseline clinical data between the two groups (p > 0.05). At the six-month follow-up, the HR-HPV clearance rates were 75.6% in the FU group and 25.6% in the observation group (p = 0.000). The LSIL regression rates were 89.5% in the FU group and 56.4% in the observation group (p = 0.000). Multivariate logistic regression analysis showed that the HR-HPV clearance rate in the FU group was 9.03 times higher than that in the observation group (95% confidence interval [CI], 3.75–21.73, p = 0.000), and the clearance rate of single-type HR-HPV infections was 5.28 times higher than that of multi-type infections (95% CI, 1.83–15.23, p = 0.002). The mean intraoperative bleeding was 1.8 ± 0.6 (1–3) mL; the mean intraoperative pain score was 2.6 ± 1.0 (1–6).Conclusions For patients with HR-HPV infection-related histological LSIL, FU can eliminate HR-HPV infection and cause lesions to regress in a short time, with few adverse effects and good tolerance.

Critical examinations of specimens, with literature reviews, have shown that Rubus davidianus is conspecific with R. lambertianus. Therefore, we treat R. davidianus as a new synonym within Rubus. We propose a new name, Rubus loirensis Ti R. Huang nom. nov. to replace the later homonym of R. pycnanthus Genev. Additionally, lectotypification of three names, R. davidianus Kuntze, R. malifolius Focke and R. viburnifolius Franch., are designated here after examination of previous works.

AbstractFreshwater lakes are subjected to increasing eutrophication and algal blooms worldwide, which have dramatically impacted the aquatic biodiversity. This situation is especially true in the Yangtze River Floodplain, China. However, few researches have been focused on differences in the spatial and temporal patterns of benthic macroinvertebrates assemblages between the two adjacent lakes in this floodplain. In this study, we conducted seasonal investigations in 2021 to compare the spatial and temporal patterns of macroinvertebrates in Lakes Taihu and Lake Chaohu. Non-metric multidimensional scaling (NMDS) analyses showed Lake Taihu was found to have differences in assemblages within the lake, but Lake Chaohu was found to have uniform assemblage across the entire lake. Macrophyte-dominated lake regions (eastern Lake Taihu) were characterised by the highest species richness and diversity indices than those in other lake regions. The pollution sensitive species (e.g. EPT: Ephemeroptera, Plecoptera and Trichoptera) were only distributed in the macrophytic areas of Lake Taihu. Corbicula fluminea, polychaetes Nephtys oligobranchia and Capitella sp. were dominant in the middle central lake regions in Lake Taihu. Lake Chaohu and the northern Lake Taihu, with turbid algal-dominated state, were characterised by dominance of Oligochaetes and Chironomids. These differences were attributed to varying habitats and environmental parameters among different lake regions. Canonical correspondence analysis (CCA) demonstrated that macrophytes, chemical oxygen demand (CODMn), temperature, ammonium (NH3-N) and electric conductivity (EC) were detected as important factors influencing such macroinvertebrate assemblage patterns between these two lakes. This study contributes to the scientific knowledge of within lake habitats, community assemblages, nutrients and pollution within these lakes.

Abstract Advanced liver cancer is the most fatal malignant cancer, and the clinical outcomes of treatment are not very satisfactory due to the complexity and heterogeneity of the tumor. Combination therapy can efficiently enhance tumor treatment by stimulating multiple pathways and regulating the tumor immune microenvironment. Nanodrug delivery systems have become attractive candidates for combined strategies for liver cancer treatment. This study reports a nano ultrasound contrast agent (arsenic trioxide (ATO)/PFH NPs@Au‐cRGD) to integrate diagnosis and treatment for efficient ultrasound imaging and liver cancer therapy. This nanodrug delivery system promotes tumor‐associated antigens release through ATO‐induced ferroptosis and photothermal‐induced immunogenic cell death, enhancing the synergistic effects of ATO and photothermal therapy in human Huh7 and mouse Hepa1–6 cells. This drug delivery system successfully activates the antitumor immune response and promotes macrophage M1 polarization in tumor microenvironment with low side effects in subcutaneous and orthotopic liver cancer. Furthermore, tumor metastasis is inhibited and long‐term immunological memory is also established in orthotopic liver cancer when the nanodrug delivery system is combined with anti‐programmed death‐ligand 1 (PD‐L1) immunotherapy. This safe nanodrug delivery system can enhance antitumor therapy, inhibit lung metastasis, and achieve visual assessment of therapeutic efficacy, providing substantial potential in clinic applications for liver cancer.

This study proposes a novel production function of digital empowerment. It constructs a theoretical framework to analyze the digital enabling process for enterprises from the production factor and economic activity aspects. It uses data mining technology to measure the degree of digitalization, extracts a typical relationship model between digitalization degree and enterprise performance, and digs out the association rules among traditional factors, digital factors, and economic activities under different relationship models. The results show that the digitalization degree and the digitalization enabling the level of mechanical and electronic enterprises are higher than those of light textile enterprises and resource-processing enterprises. The substitution elasticities and the association rules among factors and activities also have enterprise heterogeneity, which leads to differences in the digital transformation paths of different types of enterprises.

Abstract Background In the life history of Daphnia, the reproductive mode of parthenogenesis and sexual reproduction alternate in aquatic ecosystem, which are often affected by environmental and genetic factors. Recently, the sex-biased genes are of great significance for clarifying the origin and evolution of reproductive transformation and the molecular regulation mechanism of sex determination in Daphnia. Although some genes on reproductive transition of Daphnia had been researched, molecular mechanism on the maintenance of sexually dimorphic phenotypes of Daphnia are still not well known, including differentially expressed genes in different life-history stages. Results In this study, four life-history stages of Daphnia sinensis, juvenile female (JF), parthenogenetic female (PF), sexual female (SF) and male (M), were performed for transcriptome, and male-biased genes were screened. A total of 110437 transcripts were obtained and assembled into 22996 unigenes. In the four life-history stages (JF, PF, SF and M), the number of unique unigenes is respectively 2863, 445, 437 and 586, and the number of common unigenes is 9708. The differentially expressed genes (DEGs) between male and other three female stages (M vs JF, M vs PF and M vs SF) were 4570, 4358 and 2855, respectively. GO gene enrichment analysis showed that the up-regulated genes in male were mainly enriched in hydrolase activity and peptidase activity. Thirty-six genes in male were significantly higher expression than in the three female stages, including one Doublesex (Dsx) gene, one laminin gene, five trypsin genes and one serine protease genes, and one chitin synthase gene and two chitinase genes. Conclusions Our results showed that thirty-six candidate genes may be as the male-biased genes involving in the maintenance of sexually dimorphic phenotypes. This work will provide a reference for further exploring the functional genes related to sex differentiation in Daphnia species. Moreover, according to previous investigations, we thought that the expression level of functional genes may be related to the life-history stages of organisms, and may be also affected by different Daphnia species.

Objective: To evaluate the efficacy and safety of percutaneous core needle biopsy (PCNB) using ultrasound (US)-guided and contrast-enhanced ultrasound (CEUS)-guided procedures for anterior mediastinal masses (AMMs). Methods: In total, 284 consecutive patients (166 men, 118 women; mean age, 43.0 ​± ​18.4 years) who underwent PCNB for AMMs were enrolled. Patients were divided into the US-guided group (n ​= ​133) and the CEUS-guided group (n ​= ​151). PCNB was performed using a core needle (16-gauge or 18-gauge). Internal necrosis, diagnostic yield, and diagnostic accuracy were compared between the two groups. Results: The predominant final diagnosis of the cases in this study was thymoma (29.7%), lymphoma (20.5%), thymic carcinoma (13.3%), and germ cell tumour (13.3%), respectively. There was no significant difference in patient age, sex, number of percutaneous biopsies, or display rate of internal necrosis on conventional US between the two groups. The rate of internal necrosis of the lesions was significantly higher after contrast agent injection (72.2% vs. 41.7%; P ​

Background: Primary liver cancer, around 75%–85% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China, but also may re-shape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice, and improve the national average five-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Highlights We proposed RF-based radiomics analysis method by introducing three ultrasound features of direct energy attenuation (DEA), skewness of spectrum difference (SSD) and noncentrality parameter S of Rician distribution (NRD) as the feature extraction method from RF signals, investigated the effectiveness of RF-based radiomics analysis method in the immunocheckpoint prediction of programmed cell death protein 1 (PD-1), and validated the results with contrast testing of grayscale-based radiomics analysis method in this study. We also demonstrate a trend in prediction performance changes and its correlation with the number of ultrasound features. The results demonstrated that there were significant differences (p < 0.05) in radiomics scores between HCC patients with PD-1 and HCC patients without PD-1. RF-based radiomics analysis method performed well in PD-1 noninvasive preoperative prediction of HCC patients. In this study, the performance of RF-based radiomics analysis method was better than that of grayscale-based radiomics analysis method in the preoperative prediction of PD-1 in HCC patients. The AUC of DSNM, which was the RF-based radiomics analysis model with three ultrasound feature maps, reached 94.23% in the prediction of PD-1 cell protein in HCC patients.

Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4′-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves’ amplitude. The most promising compound 10e showed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound 10e was able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound 10e even showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound 10e did not block the hERG potassium channel which highly associated with cardiotoxicity.

Objective: This study aimed to investigate the application value of contrast-enhanced ultrasound (CEUS) before and after minimally invasive ablation procedures for benign thyroid nodule(s) (BTN). Methods: This prospective study included patients with BTNs scheduled to undergo ultrasound-guided minimally invasive ablation treatment. CEUS was performed before and after ablation (at 1 day, and 1, 6, and 12 months after ablation). Changes in microvascular perfusion and the volume of BTNs were noted and assessed. Results: Sixty-two patients (62 BTNs), who underwent ablation procedures between June 2016 and August 2020, were included. All lesions were confirmed by biopsy, and histopathological results were obtained before ablation treatment. On preoperative CEUS, the lesions exhibited hyperenhancement (53.23%) or iso-enhancement (46.77%) during the arterial phase, and all lesions exhibited iso-enhancement in the venous and late phases. One day after ablation, none of the BTNs exhibited obvious enhancement on CEUS. One (1.61%) lesion was re-treated due to a nodule-like enhancement area detected by CEUS at the 6-month follow-up. The mean nodular volume reduction rate (VRR) at 1, 6, and 12 months follow-up demonstrated no significant difference between the two ablation groups (microwave ablation versus radiofrequency ablation). Twelve months after ablation, the mean (±SD) VRR of all BTNs was 60.3 ​± ​10.3%. Conclusion: CEUS helped guide treatment decisions for BTNs before ablation treatment. Moreover, it could also be used to accurately and noninvasively evaluate treatment efficacy.

Objective To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with a high-grade squamous intraepithelial lesion (HSIL) 12 months after focused ultrasound (FUS) or loop electrosurgical excision procedure (LEEP), and analyze the influencing factors. Methods A retrospective cohort was established in HSIL patients with HR-HPV infection treated with FUS or LEEP from 2015 to 2019. The cohort consisted of 321 patients under 30 years of age, of which 119 patients received FUS and 202 patients received LEEP. The Cox regression model was used to identify the influencing factors for HR-HPV clearance. Kaplan–Meier method was applied to estimate the efficacy of FUS and LEEP in HR-HPV clearance, and the log-rank test was used to compare the efficacy difference between FUS and LEEP. Results Multivariate Cox regression analysis showed that both FUS and LEEP were independent influencing factors for HR-HPV clearance. HR-HPV cleared faster in the FUS group than in the LEEP group [the median time to HR-HPV clearance: 6 months in the FUS group (95% CI: 5.492–6.508) and 6 months in the LEEP group (95% CI: 5.734–6.266), p = 0.021]. The HR-HPV clearance rates at 6 and 12 months were 54.6% and 94.1% respectively in the FUS group, and 50.5% and 79. 2%, respectively in the LEEP group (p = 0.001 at 6 months, p = 0.000 at 12 months). Conclusions For HPV-positive HSIL patients under 30, FUS had a better HR-HPV clearance effect than LEEP 1 year after treatment. FUS may be a viable modality for the treatment of young HSIL patients.

Thermal ablation (TA), as a minimally invasive therapeutic technique, has been extensively used to the treatment of solid tumors, such as renal cell carcinoma (RCC), which, unfortunately, still fails to overcome the high risk of local recurrence and distant metastasis since the incomplete ablation cannot be ignored due to various factors such as the indistinguishable tumor margins and limited ablation zone. Herein, we report the injectable thermosensitive hydrogel by confining curcumin (Cur)-loaded hollow mesoporous organosilica nanoparticles (Cur@HMON@gel) which can locate in tumor site more than half a month and mop up the residual RCC under ultrasound (US) irradiation after transforming from colloidal sol status to elastic gel matrix at physiological temperature. Based on the US-triggered accelerated diffusion of the model chemotherapy drug with multi-pharmacologic functions, the sustained and controlled release of Cur has been demonstrated in vitro. Significantly, US is employed as an external energy to trigger Cur, as a sonosensitizer also, to generate reactive oxygen species (ROS) for sonodynamic tumor therapy (SDT) in parallel. Tracking by the three-dimensional contrast-enhanced ultrasound (3D-CEUS) imaging, the typical decreased blood perfusions have been observed since the residual xenograft tumor after incomplete TA were effectively suppressed during the chemo-sonodynamic therapy process. The high in vivo biocompatibility and biodegradability of the multifunctional nanoplatform confined by thermogel provide the potential of their further clinical translation for the solid tumor eradication under the guidance and monitoring of 3D-CEUS.

BackgroundAn increasing number of lung cancer patients are opting for lobectomy for oncological treatment. However, due to the unique organismal condition of elderly patients, their short-term postoperative mortality is significantly higher than that of non-elderly patients. Therefore, there is a need to develop a personalised predictive tool to assess the risk of postoperative mortality in elderly patients.MethodsInformation on the diagnosis and survival of 35,411 older patients with confirmed lobectomy NSCLC from 2009 to 2019 was screened from the SEER database. The surgical group was divided into a high-risk mortality population group (≤90 days) and a non-high-risk mortality population group using a 90-day criterion. Survival curves were plotted using the Kaplan-Meier method to compare the differences in overall survival (OS) and lung cancer-specific survival (LCSS) between the two groups. The data set was split into modelling and validation groups in a ratio of 7.5:2.5, and model risk predictors of postoperative death in elderly patients with NSCLC were screened using univariate and multifactorial logistic regression. Columnar plots were constructed for model visualisation, and the area under the subject operating characteristic curve (AUC), DCA decision curve and clinical impact curve were used to assess model predictiveness and clinical utility.ResultsMulti-factor logistic regression results showed that sex, age, race, histology and grade were independent predictors of the risk of postoperative death in elderly patients with NSCLC. The above factors were imported into R software to construct a line graph model for predicting the risk of postoperative death in elderly patients with NSCLC. The AUCs of the modelling and validation groups were 0.711 and 0.713 respectively, indicating that the model performed well in terms of predictive performance. The DCA decision curve and clinical impact curve showed that the model had a high net clinical benefit and was of clinical application.ConclusionThe construction and validation of a predictive model for death within 90 days of lobectomy in elderly patients with lung cancer will help the clinic to identify high-risk groups and give timely intervention or adjust treatment decisions.

Objective The purpose of this study was to compare the efficacy of focused ultrasound (FU) and interferon drug therapy for cervical intraepithelial neoplasia 1 (CIN1) and chronic cervicitis associated with high risk human papillomavirus (HR-HPV) infection, as well as analyze the influencing factors. Methods A retrospective cohort study was performed from January 2017 to December 2019. A total of 592 patients were enrolled, of which 300 patients were treated with FU and 292 patients were treated with interferon drugs. Kaplan-Meier curves and a COX regression model were used to compare the curative effects of the two therapeutic methods using HR-HPV clearance as the main outcome. The relationship between age, HR-HPV infection type, pathological type, preoperative HR-HPV status and HR-HPV clearance were also analyzed. Results The median time for HR-HPV clearance was 6.00 months (95% CI: 5.24–6.76) in the FU group and 26.00 months (95% CI: 22.32–29.68) in the medication group. A significant difference was observed between the two groups (χ2 =198.902, p = 0.000). The HR-HPV clearance rate was 4.927 (95% CI 3.840–6.321; p = 0.000) times higher in the patients treated with FU than those treated with interferon drugs. In the FU group, no significant difference was observed in HR-HPV clearance rate between CIN1 and chronic cervicitis (χ2=0.660, p = 0.416), which was also insignificant between HR-HPV persistent and non-persistent infections (χ2=0.751, p = 0.386). Conclusion FU therapy can eliminate HR-HPV infections in a short period of time. Moreover, the treatment efficacy of FU was significantly superior to that of interferon drugs.

BackgroundNodular thyroid disease is by far the most common thyroid disease and is closely associated with the development of thyroid cancer. Coal miners with chronic coal dust exposure are at higher risk of developing nodular thyroid disease. There are few studies that use machine learning models to predict the occurrence of nodular thyroid disease in coal miners. The aim of this study was to predict the high risk of nodular thyroid disease in coal miners based on five different Machine learning (ML) models.MethodsThis is a retrospective clinical study in which 1,708 coal miners who were examined at the Huaihe Energy Occupational Disease Control Hospital in Anhui Province in April 2021 were selected and their clinical physical examination data, including general information, laboratory tests and imaging findings, were collected. A synthetic minority oversampling technique (SMOTE) was used for sample balancing, and the data set was randomly split into a training and Test dataset in a ratio of 8:2. Lasso regression and correlation heat map were used to screen the predictors of the models, and five ML models, including Extreme Gradient Augmentation (XGBoost), Logistic Classification (LR), Gaussian Parsimonious Bayesian Classification (GNB), Neural Network Classification (MLP), and Complementary Parsimonious Bayesian Classification (CNB) for their predictive efficacy, and the model with the highest AUC was selected as the optimal model for predicting the occurrence of nodular thyroid disease in coal miners.ResultLasso regression analysis showed Age, H-DLC, HCT, MCH, PLT, and GGT as predictor variables for the ML models; in addition, heat maps showed no significant correlation between the six variables. In the prediction of nodular thyroid disease, the AUC results of the five ML models, XGBoost (0.892), LR (0.577), GNB (0.603), MLP (0.601), and CNB (0.543), with the XGBoost model having the largest AUC, the model can be applied in clinical practice.ConclusionIn this research, all five ML models were found to predict the risk of nodular thyroid disease in coal miners, with the XGBoost model having the best overall predictive performance. The model can assist clinicians in quickly and accurately predicting the occurrence of nodular thyroid disease in coal miners, and in adopting individualized clinical prevention and treatment strategies.

Harnessing commonsense knowledge poses a significant challenge for machine comprehension systems. This paper primarily focuses on incorporating a specific subset of commonsense knowledge, namely, script knowledge. Script knowledge is about sequences of actions that are typically performed by individuals in everyday life. Our experiments were centered around the MCScript dataset, which was the basis of the SemEval-2018 Task 11: Machine Comprehension using Commonsense Knowledge. As a baseline, we utilized our Three-Way Attentive Networks (TriANs) framework to model the interactions among passages, questions, and answers. Building upon the TriAN, we proposed to: (1) integrate a pre-trained language model to capture script knowledge; (2) introduce multi-layer attention to facilitate multi-hop reasoning; and (3) incorporate positional embeddings to enhance the model’s capacity for event-ordering reasoning. In this paper, we present our proposed methods and prove their efficacy in improving script knowledge integration and reasoning.

In contrast to diradical linked by π-conjugation, there have been only a limited number of studies reported for those linked by homoconjugation systems. Bis(nitronyl nitroxide) diradicals and monoradical connected by a core non-rigid triptycene unit were synthesized. EPR spectroscopy and SQUID were employed to investigate the magnetic exchange interactions. The results demonstrate that the values of ΔEST are 0.19 kcal/mol (J = 34.4 cm−1) for 2,6-TP-NN and −0.21 kcal/mol (J = −36.9 cm−1) for 2,7-TP-NN, indicating ferromagnetic interaction and antiferromagnetic interaction, respectively. The spin polarization rule is not a precise predictor of the behavior of triptycene diradicals, and therefore, we improve the model. The experimental findings indicate that homoconjugation can function directly as a coupling pathway between the two spin centers, which is in qualitative agreement with the DFT theoretical calculations and the Borden rule. This research has found a special means of achieving spin coupling in non-rigid aromatics by means of homoconjugation.

As the popularity of large language models (LLMs) has risen over the course of the last year, led by GPT-3/4 and especially its productization as ChatGPT, we have witnessed the extensive application of LLMs to text summarization. However, LLMs do not intrinsically have the power to verify the correctness of the information they supply and generate. This research introduces a novel approach to abstractive summarization, aiming to address the limitations of LLMs in that they struggle to understand the truth. The proposed method leverages extracted knowledge graph information and structured semantics as a guide for summarization. Building upon BART, one of the state-of-the-art sequence-to-sequence pre-trained LLMs, multi-source transformer modules are developed as an encoder, which are capable of processing textual and graphical inputs. Decoding is performed based on this enriched encoding to enhance the summary quality. The Wiki-Sum dataset, derived from Wikipedia text dumps, is introduced for evaluation purposes. Comparative experiments with baseline models demonstrate the strengths of the proposed approach in generating informative and relevant summaries. We conclude by presenting our insights into utilizing LLMs with graph external information, which will become a powerful aid towards the goal of factually correct and verified LLMs.

Abstract This study aimed to evaluate and compare the accuracy of average faces constructed by different methods. Original three-dimensional facial images of 26 adults in Chinese ethnicity were imported into Di3DView and MorphAnalyser for image processing. Six average faces (Ave_D15, Ave_D24, Ave_MG15, Ave_MG24, Ave_MO15, Ave_MO24) were constructed using “surface-based registration” method with different number of landmarks and template meshes. Topographic analysis was performed, and the accuracy of six average faces was assessed by linear and angular parameters in correspondence with arithmetic means calculated from individual original images. Among the six average faces constructed by the two systems, Ave_MG15 had the highest accuracy in comparison with the conventional method, while Ave_D15 had the least accuracy. Other average faces were comparable regarding the number of discrepant parameters with clinical significance. However, marginal and non-registered areas were the most inaccurate regions using Di3DView. For MorphAnalyser, the type of template mesh had an effect on the accuracy of the final 3D average face, but additional landmarks did not improve the accuracy. This study highlights the importance of validating software packages and determining the degree of accuracy, as well as the variables which may affect the result.

A novel one-dimensional malleable spin-crossover (SCO) complex {[Fe(MPEG-trz)3](BF4)2} has been successfully synthesized by molecular self-assembly between 4-amino-1,2,4-triazoles (MPEG-trz) grafted with a long flexible chain methoxy polyethylene glycol (MPEG) and metallic complex Fe(BF4)2•6H2O. The detailed structure information was illustrated by using FT-IR and 1H NMR measurements, while the physical behaviors of the malleable SCO complexes were systematically investigated by using magnetic susceptibility measurements using superconductivity quantum interference device (SQUID) and differential scanning calorimetry (DSC). This new metallopolymer exhibits a remarkable spin crossover transition behavior, between two spin quantum states (Fe2+ ions): high spin (HS) state (quintet state) and low spin (LS) state (singlet state), at a specific critical temperature with a slender hysteresis loop of 1 K. DFT computations revealed the partial rules of HOMO-LUMO energy levels and spin density distributions of different four-position substituted [Fe(1,2,4-triazole)3]2+ derivatives with different length of repeat units in polymer complexes. This can go a step further to depict the spin and magnetic transition behaviors of SCO polymer complexes. Furthermore, the coordination polymers possess an excellent processability due to an outstanding malleability, which can be easily shaped into a polymer film with spin magnetic switching properties.

Objective The aim of this study was to evaluate changes in anti-Müllerian hormone (AMH) levels after ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment of cesarean scar pregnancy (CSP). Methods A retrospective case series study was conducted in the Affiliated Hospital of North Sichuan Medical College. Thirty-two women with cesarean scar pregnancy who met the inclusion criteria were enrolled in the study between January 2018 and December 2019. All patients underwent USgHIFU treatment with or without suction curettage. Intraoperative blood loss in suction curettage and hysteroscopy procedures, time to return of β-human chorionic gonadotropin (β-hCG) to normal levels, and time to recovery of normal menstruation were recorded. AMH levels before and 3 months after HIFU treatment were compared to determine whether USgHIFU treatment affected ovarian reserve. Results AMH levels before and 3 months after HIFU ablation were 1.87 ± 1.19 ng/ml and 1.90 ± 1.17 ng/ml, respectively. There was no significant difference in AMH levels between the two-time points (p > .05). The median volume of intraoperative blood loss was 20 ml, the median time for the serum β-hCG level to return to normal was 35.5 days, and the median time of menstruation recovery was 39 days. Conclusions USgHIFU treatment for CSP was effective and safe without affecting ovarian reserve.

BackgroundImmunotherapy has become a pillar of advanced solid tumors treatment. Patients are more likely to benefit from neoadjuvant immunotherapy compared with traditional neoadjuvant therapy. However, the safety and efficacy of neoadjuvant immunotherapy for the treatment of locally advanced, surgically resectable Esophageal squamous cell carcinoma (ESCC) remain unknown.MethodESCC patients who received neoadjuvant treatment following minimally invasive esophagogastrostomy were enrolled from June 2020 to September 2021. The characteristics of neoadjuvant treatment and surgery were investigated to determine the safety and efficacy of the neoadjuvant combination of chemotherapy and immunotherapy (NCI).ResultsA total of 149 patients were included in the study. Patient ratio was 40:109 between NCI and neoadjuvant chemotherapy plus radiotherapy (NCR) groups. No significant difference was found in terms of pathological characteristics, including ypN stage, ypTNM stage, differentiation, lymphovascular invasion, perineural invasion, pathological complete regression and tumor regression score, and these parameters were not correlated with NCI or NCR (all p>0.05). Regarding to the operation, the NCI group had less blood loss (49.25 ± 13.47 vs. 57.02 ± 47.26, p2 perioperative complications (p=0.042) than the NCR group.ConclusionOverall, the findings reported here indicate NCI could result in better outcome and less complications to locally advanced ESCC patients compared with NCR therapy. As a novel therapeutic option, the efficacy and safety of NCI appears to be feasible and safe, while long-term survival data is still needed.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

Abstract Background The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies. Methods The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis. Results The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses. Conclusions This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.

Abstract Background Biomarkers of clinical efficacy for subcutaneous immunotherapy (SCIT) on allergic rhinitis (AR) have not been identified yet. This study aims to assess the clinical relevance of serum inhibitory activity for IgE by the method of enzyme-linked immunosorbent facilitated antigen binding (ELIFAB) during SCIT for Artemisia-sensitized AR patients. Methods 19 AR patients were studied who had undergone Artemisia-specific SCIT for more than 8 months (19.68 months on average, ranging from 9 to 33 months). Peripheral bloods were collected before and after treatment. The serum inhibitory activity for IgE was tested by ELIFAB and the level of Artemisia-specific IgG4 (Artemisia-sIgG4) was determined by ELISA. Clinical improvement was evaluated based on the symptom scores and rescue medication use (SMS). The 2-tailed Wilcoxon signed-rank test and the Spearman rank test (two-tailed) were used to analyze data by using SPSS 20.0, with P values of less than 0.05 considered as significant. Results The SMS decreased significantly after SCIT (before: 12.79 ± 4.250, after: 6.11 ± 3.828, P = 0.000