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Recent developments in electrochemical biosensors (ECBSs) for real-time disease diagnosis and point-of-care testing in saliva via relevant biomarker detection are reviewed.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, and the prognosis of HCC patients with lymph node metastasis (LNM) is poor. However, robust biomarkers for predicting the prognosis of HCC LNM are still lacking. This study used weighted gene coexpression network analysis of GSE28248 ( N = 80 ) microarray data to identify gene modules associated with HCC LNM and validated in GSE40367 dataset ( N = 18 ). The prognosis-related genes in the HCC LNM module were further screened based on the prognostic curves of 371 HCC samples from TCGA. We finally developed a prognostic signature, PSG-30, as a prognostic-related biomarker in HCC LNM. The HCC subtypes identified by PSG-30-based consensus clustering analysis showed significant differences in prognosis, clinicopathological stage, m6A modification, ferroptosis activation, and immune characteristics. In addition, RAD54B was selected by regression model as an independent risk factor affecting the prognosis of HCC patients with LNM, and its expression was significantly positively correlated with tumor mutational burden and microsatellite instability in high-risk subtypes. Patients with high RAD54B expression had a better prognosis in the immune checkpoint inhibitor-treated cohorts but had a poor prognosis in the HCC sorafenib-treated group. The association of high RAD54B expression with LNM in breast cancer (BRCA) and cholangiocarcinoma and its prognostic effect in BRCA LNM cases suggest the value of RAD54B at the pancancer level. In conclusion, PSG-30 can effectively identify HCC LNM population with poor prognosis, and high-risk patients with high RAD54B expression may be more suitable for immunotherapy.

Background Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. Results In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. Conclusions The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

A crown-ether clathrate employing a rare-earth ion as the central metal ion was developed, and shown to display switchable dielectric behaviours around a temperature of about 230 K.

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, and distant metastasis is a critical factor in the prognosis of patients with GC. Understanding the mechanism of GC metastasis will help improve patient prognosis. Studies have confirmed that urokinase-type plasminogen activator receptor (PLAUR) promotes GC metastasis; however, its relationship with anoikis resistance and associated mechanisms remains unclear. In this study, we demonstrated that PLAUR promotes the anoikis resistance and metastasis of GC cells and identified transcription Factor 7 Like 2 (TCF7L2) as an important transcriptional regulator of PLAUR. We also revealed that TCF7L2 is highly expressed in GC and promotes the anoikis resistance and metastasis of GC cells. Moreover, we found that TCF7L2 transcription activates PLAUR. Finally, we confirmed that TCF7L2 is an independent risk factor for poor prognosis of patients with GC. Our results show that TCF7L2 and PLAUR are candidate targets for developing therapeutic strategies for GC metastasis.

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In recent years, the incidences and mortalities from colorectal cancer (CRC) have been increasing; therefore, there is an urgent need to discover newer drugs that enhance drug sensitivity and reverse drug tolerance in CRC treatment. With this view, the current study focuses on understanding the mechanism of CRC chemoresistance to the drug as well as exploring the potential of different traditional Chinese medicine (TCM) in restoring the sensitivity of CRC to chemotherapeutic drugs. Moreover, the mechanism involved in restoring sensitivity, such as by acting on the target of traditional chemical drugs, assisting drug activation, increasing intracellular accumulation of anticancer drugs, improving tumor microenvironment, relieving immunosuppression, and erasing reversible modification like methylation, have been thoroughly discussed. Furthermore, the effect of TCM along with anticancer drugs in reducing toxicity, increasing efficiency, mediating new ways of cell death, and effectively blocking the drug resistance mechanism has been studied. We aimed to explore the potential of TCM as a sensitizer of anti-CRC drugs for the development of a new natural, less-toxic, and highly effective sensitizer to CRC chemoresistance.

Objective: The study aimed to assess the efficacy and safety of clinical trials of biologics in improving the salivary gland (SG) function in primary Sjögren’s syndrome (pSS), which has not been analyzed critically and systematically.Methods: PubMed, Web of Science, ClinicalTrials.gov, the EU Clinical Trials Register, and the Cochrane Library were searched for clinical trials that reported effects of biological treatment on the SG function and safety in pSS patients. Inclusion criteria were defined following participants, interventions, comparisons, outcome, and study design (PICOS) recommendations. The objective index (the change of unstimulated whole saliva (UWS) flow) and the serious adverse event (SAE) were assessed as main outcome measures. A meta-analysis of the efficacy and safety of the treatment was conducted. Quality assessment, sensitivity analysis, and publication bias were assessed. The effect size together with a 95% confidence interval was used to estimate the efficacy and safety of biological treatment and was plotted as a forest plot.Results: The literature search yielded 6,678 studies, nine of which fulfilled the inclusion criteria, with seven randomized controlled trials (RCTs) and two non-RCT clinical studies. Generally, biologics do not significantly increase UWS from the baseline of pSS patients compared to the control group at a matched time point (p = 0.55; standard mean difference, SMD = 0.05; 95% confidence interval, CI: −0.11 and 0.21). However, pSS patients with shorter disease duration (≤3 years; SMD = 0.46; 95% CI: 0.06 and 0.85) were prone to have a better response to biological treatment by showing higher increased UWS than patients with longer disease duration (> 3 years; SMD = −0.03; 95% CI: −0.21 and 0.15) (p = 0.03). For the meta-analysis of the safety of biological treatment, the SAEs in the biologics group were significantly higher than those of the control group (p = 0.0021; log odds ratio, OR = 1.03; 95% CI: 0.37 and 1.69).Conclusion: Biological intervention during the early course of the disease may benefit pSS patients better than that during the late course. Significantly, more SAEs in the biologics group indicate that the safety of biologics needs to be addressed for future biological clinical trials and treatment.

Purpose A comparative retrospective study to assess the impact of PSMA Ligand PET/MRI ([68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 PET/MRI) as a new method of target delineation compared to conventional imaging on whole-pelvis radiotherapy for high-risk prostate cancer (PCa). Patients and methods Forty-nine patients with primary high-risk PCa completed the whole-pelvis radiotherapy plan based on PSMA PET/MRI and MRI. The primary endpoint compared the size and overlap of clinical target volume (CTV) and nodal gross tumour volume (GTVn) based on PSMA PET/MRI and MRI. The diagnostic performance of two methods for pelvic lymph node metastasis (PLNM) was evaluated. Results In the radiotherapy planning for high-risk PCa patients, there was a significant correlation between MRI-CTV and PET/MRI-CTV (P = 0.005), as well as between MRI-GTVn and PET/MRI-GTVn (P P = 0.660, P = 0.650, respectively). The conformity index (CI), lesion coverage factor (LCF) and Dice similarity coefficient (DSC) of CTVs were 0.999, 0.953 and 0.954. The CI, LCF and DSC of GTVns were 0.927, 0.284, and 0.32. Based on pathological lymph node analysis of 463 lymph nodes from 37 patients, the sensitivity, specificity of PET/MRI in the diagnosis of PLNM were 77.78% and 99.76%, respectively, which were higher than those of MRI (P = 0.011). Eight high-risk PCa patients who finished PSMA PET/MRI changed their N or M stage. Conclusion The CTV delineated based on PET/MRI and MRI differ little. The GTVn delineated based on PET/MRI encompasses metastatic pelvic lymph nodes more accurately than MRI and avoids covering pelvic lymph nodes without metastasis. We emphasize the utility of PET/MRI fusion images in GTVn delineation in whole pelvic radiotherapy for PCa. The use of PSMA PET/MRI aids in the realization of more individual and precise radiotherapy for PCa.

Supplementary Material 2

Additional file 1: Figure S1. Study diagram. Figure S2. Incidence of grade 3 diarrhea during neoadjuvant treatment. Table S1. Clinical responses following neoadjuvant treatment assessed by local investigator per RECIST v1.1. Table S2. Exposure of the individual components of study treatment. Table S3. Serious adverse events during neoadjuvant therapy. Table S4. Summary of data on diarrhea during neoadjuvant treatment. Table S5. Characteristics of diarrhea before and after proactive management. Table S6. Overview of neutropenia, febrile neutropenia, and decreased white blood cell count during neoadjuvant treatment period.

Additional file 2: Figure S1. Distribution of 17-mer depth for estimating the genome size. The x-axis represents k-mer depths while y-axis represents the proportions. The blue line represents the proportion of 17-mer in each depth. The peak depth is at 25-fold and total number of 17-mer is 61,791,522,108. The South China tiger (P. t. amoyensis) genome size was estimated to be 2471.66 Mb from the formula: Genome size = K-mer_number/K_depth of peak. Figure S2. Hi-C chromosomal contact heat map. A 500 kb resolution was used to calculate the number of Hi-C read pairs in any two bins. Figure S3. The collinearity between the South China tiger and domestic cat (Felis catus) genomes. Each dot represents an aligned region while the minimum length is 10 kb. The red dot represents forward comparison and the blue dot reverse comparison. Figure S4. Q30 and GC content for each sample. The average Q30 and GC content are 93.24% and 42.04%, respectively. Their very low variation reflected our re-sequencing data to be high quality. Figure S5. The distribution of mapping rates and average mapping depths for each individual. The depths ranged from 12.91× to 18.96 × while the rates varied from 96.03% to 98.92%. Figure S6. The distribution of the SNP number and frequency. Number of genome-wide SNPs (top) and frequency of SNPs per 1 kb of each tiger sample (bottom). Figure S7. Nucleotide diversity π estimates of six tiger subspecies. Figure S8. Heterozygosity statistics of genome-wide SNPs. (a) Observed heterozygosity across all individual genomes of each tiger subspecies. (b) Genomic heterozygosity in each tiger subspecies at population level. Figure S9. Pairwise FST values between six tiger subspecies. The weighted FST values are shown above the diagonal while their standard deviations below the diagonal. Figure S10. Principal component analysis using genome-wide SNPs of six tiger subspecies. Figure S11. A maximum likelihood tree was built using TreeMix software with whole-genome sequencing data of six tiger subspecies and cat. Figure S12. Cluster analysis based on the matrix of genome-wide identity-by-state (IBS) pairwise distances between six tiger subspecies determined by a permutation score. Figure S13. Analysis of genome-wide average identity-by-state (IBS) pairwise identities between six tiger subspecies. Figure S14. Population genetic structure of the South China tigers estimated by the ADMIXTURE. Figure S15. Demographic histories of tiger subspecies. PSMC analysis shows the change in effective population size over time. The dash lines represent 100 bootstraps. The representative individuals sequenced at a high read coverage were selected for each graph, South China tiger (ptam_4, mean 25.38×), Amur tiger (ptal_1, mean 14.76×), Indochinese tiger (ptco_2, mean 13.98×), Malayan tiger (ptja_7, mean 13.13×), Bengal tiger (ptti_3, mean 13.79×), and Sumatran tiger (ptsu_1, mean 13.41×). Figure S16. The results of Dsuite. Heatmap showing statistical support for introgression between pairs of tiger subspecies. Cells in the heatmap indicate the pairwise Z score values between the branch b identified on the expanded tree on the Y axis (relative to its sister branch) and the taxa P3 identified on the X-axis. The grey color indicates the none. (a) Result of branch for South China tiger (lineage 1) with the other tiger subspecies populations. (b) Result of branch for South China tiger (lineage 2) with the other tiger subspecies populations. (c) Result of branch for South China tiger (ptam1 individual) with the other tiger subspecies populations. Figure S17. The graph of ABBA-BABA test. The values of D (pop1, pop2; pop3, pop4) >0 indicates that there are gene flows between pop1 and pop3. Here, only the introgression occurred in South China tiger will be shown. (a) D-statistic for South China tiger (lineage 1) with other tiger subspecies. (b) D-statistic for South China tiger (lineage 2) with other tiger subspecies. (c) D-statistic for South China tiger (ptam1 individual) with other tiger subspecies. Figure S18. Plot of inferred introgression between the South China tiger lineage 1 and other tiger subspecies populations detected by the TreeMix method. The scale bar shows 10 times the average standard error of the entries in the sample covariance matrix. Figure S19. Plot of inferred introgression between the South China tiger lineage 2 and other tiger subspecies populations detected by the TreeMix method. The scale bar shows 10 times the average standard error of the entries in the sample covariance matrix. Figure S20. Plot of inferred introgression between the South China tiger ptam_1 individual and other tiger subspecies populations detected by the TreeMix method. The scale bar shows 10 times the average standard error of the entries in the sample covariance matrix. Figure S21. Genomic inbreeding coefficients FH in each tiger subspecies. Figure S22. The plot of three inbreeding coefficients (FP, FH, and FROH) of the South China tiger. Figure S23. Comparison of homozygote and heterozygote percentage of per mutation category among six tiger subspecies. The significant value was calculated by t-test.

Supplementary Material 1

For high-precision position and angle control in robots, it is essential to compensate for the hysteretic behaviour caused by friction when the motion direction is reversed. An accurate friction model which is suitable for control system analysis and implementation is highly desirable. A differential model is proposed in the current paper for the modelling of hysteresis effects caused by friction phenomena. The model is constructed by employing a phenomenological phase-transition theory to mimic the friction mechanism. The bristle friction mechanism is adapted. The switching between static and dynamic friction is regarded as a reversible phase-transition phenomenon, which could be characterized by the local minima of a non-convex potential energy function. The Stribeck effect and the hysteretic relation between friction and velocity are modelled by a nonlinear ordinary differential equation. The comparison of the numerical simulation results and existing experimental friction data are presented. It is illustrated that the friction hysteresis loops are well captured, the capability of the proposed model is verified.

Introduction This study proposes a novel data pipeline based on micro–computed tomographic (micro-CT) data for training the U-Net network to realize the automatic and accurate segmentation of the pulp cavity and tooth on cone-beam computed tomographic (CBCT) images. Methods We collected CBCT data and micro-CT data of 30 teeth. CBCT data were processed and transformed into small field of view and high-resolution CBCT images of each tooth. Twenty-five sets were randomly assigned to the training set and the remaining 5 sets to the test set. We used 2 data pipelines for U-Net network training: one manually labeled by an endodontic specialist as the control group and one processed from the micro-CT data as the experimental group. The 3-dimensional models constructed using micro-CT data in the test set were taken as the ground truth. The Dice similarity coefficient, precision rate, recall rate, average symmetric surface distance, Hausdorff distance, and morphologic analysis were used for performance evaluation. Results The segmentation accuracy of the experimental group measured by the Dice similarity coefficient, precision rate, recall rate, average symmetric surface distance, and Hausdorff distance were 96.20% ± 0.58%, 97.31% ± 0.38%, 95.11% ± 0.97%, 0.09 ± 0.01 mm, and 1.54 ± 0.51 mm in the tooth and 86.75% ± 2.42%, 84.45% ± 7.77%, 89.94% ± 4.56%, 0.08 ± 0.02 mm, and 1.99 ± 0.67 mm in the pulp cavity, respectively, which were better than the control group. Morphologic analysis suggested the segmentation results of the experimental group were better than those of the control group. Conclusions This study proposed an automatic and accurate approach for tooth and pulp cavity segmentation on CBCT images, which can be applied in research and clinical tasks.

Purpose- The aim of this study is to analyze the effect of corporate social responsibility (CSR) and social preference on quality improvement of the agricultural products supply chain composed of agricultural products producer and processor (A3P) and supermarket by theoretical analysis and empirical evidence. Methodology- This paper sets Stackelberg game model under A3P’s CSR by considering supermarket’s altruistic reciprocity and A3P’s fairness conern, respectively. By comparative analysis, we study the effect of CSR, altruistic reciprocity and fairness conern on the quality improvement of the agricultural products supply chain. Then, we adopt the empirical evidence to analyze the correlation between CSR, altruistic reciprocity (fairness concern) and quality improvement and the mediating effect of altruistic reciprocity (fairness concern) by investigating the agricultural enterprises.

As a common autoimmune disease with the characteristic of early complication, primary biliary cholangitis (PBC) leads to an increasing number of mortalities among people with end-stage liver disease (ESLD) waiting for liver transplantation. Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for PBC, and a good response to treatment could acquire an ideal prognosis. Patients with poor UDCA response usually have more adverse outcomes and worse survival, therefore, the management of this group become a major consideration.Due to the complexity of race and environment for PBC, different criteria for UDCA response exhibit various predictive performances. Factors affecting UDCA response conditions include gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities, while no agreement has been reached. In this review, we mainly focus on cellular senescence, immune-mediated damage, and vitamin D deficiency as possible mechanisms for UDCA non-responders.The pathogenesis of PBC has yet to be clarified. Immunology-related mechanisms and therapy targets ought to be the main effort made for further study. Irrespective of the response condition, UDCA is recommended for routine administration in all PBC patients without contraindication. Ongoing clinical trials of second-line and additional therapy exhibit promising prospects.

In recent years, there has been an increasingly heated debate on whether Chinese dark tea is contaminated with mycotoxins and whether it poses health risks to consumers. In this study, a rapid method based on high-performance liquid chromatography was used to detect ochratoxin A (OTA) in Chinese dark tea samples from different regions of China and different years. Of the 228 Chinese dark tea samples tested, 21 were detected for OTA contamination, with a concentration ranging from 2.51 ± 0.16 to 12.62 ± 0.72 μg/kg. Subsequently, a dark tea drinking risk assessment was conducted, and the hazard quotient for each group was far below the acceptable level of 1.0. Of the 12 Aspergillus spp. strains isolated, one strain of Aspergillus niger had the ability to produce OTA. We also found that tea polyphenols and epigallocatechin gallate inhibited the growth of ochratoxin-producing Aspergillus niger and the expression of non-ribosomal peptide synthetase (NRPS), a key gene for ochratoxin synthesis. Thus, OTA contamination of dark tea is at an acceptable risk level, and the inhibition of ochratoxigenic Aspergillus niger by polyphenols provides new insights into the safety of dark tea consumption.

A new flavonoid glycoside, luteolin-3'

Background We analysed the survival of colorectal cancer (CRC) patients with lung metastasis and lung-only metastasis and determined the risk factors for lung metastasis in CRC patients. Methods Data from colorectal cancer patients with lung metastasis diagnosed from 2010 to 2015 were obtained from the SEER database. Survival was analysed using the Kaplan–Meier method and log-rank test, the Cox proportional hazards regression model, and a competing risk model. The predictive ability of the nomgram was assessed by the concordance index (C-index) and calibration curves. The data from the SEER database for the period 2016–2019 was used as an external validation set. The characteristics of 70 CRC patients treated at Shanghai East Hospital between 2016 and 2019 were retrospectively analysed and data from China was chosen as an external validation set. Results The median survival time for colorectal cancer patients with lung metastasis was 12 months, while this value was 24 months in patients with lung-only metastasis. Among all CRC patients with lung metastasis, age, grade, T stage, N stage, presence of liver, brain or bone metastasis, anatomic site and surgery were related to overall survival (OS). In CRC patients with lung-only metastasis, age, T stage, marital status, chemotherapy and surgery were independent prognostic factors affecting OS. Two nomograms predicting OS were established, with great discrimination (C-index between 0.67 and 0.81) and excellent calibration. Factors including age, race, sex, tumour grade, T stage, N stage, presence of liver, brain or bone metastasis, marital status, insurance status and anatomic location were related to the occurrence of lung metastasis in CRC patients. Conclusion We developed two reliable clinical prediction models among CRC patients to predict the OS rates in patients with lung metastasis and lung metastasis only.

Perennial ryegrass (Lolium perenne) is a cool-season turf and forage grass. Heat shock transcription factors (HSFs) play an important role in regulating plant abiotic stress. However, HSFs in perennial ryegrass have rarely been characterized. Here, 25 LpHSFs were identified from the perennial ryegrass genome. Phylogenetic analysis showed that the LpHSFs could be classified into 12 subclasses. Gene structure analysis showed that 22 LpHSFs have only one intron. Cis-acting elements analysis revealed that the promoter of 15 LpHSFs contained hormone responsive and abiotic stress responsive elements. Expression profile analysis indicated that 24 LpHSFs were differentially expressed under submerge, drought, heat and cold stresses. In addition, a subclass C2 gene, LpHSFC2b, was significantly induced by abiotic stresses. The LpHSFC2b protein is localized to the nucleus, and heterologous expression of LpHSFC2b in Arabidopsis improves plant thermotolerance. This study provides insights useful for breeding of stress tolerance in perennial ryegrass. This article is protected by copyright. All rights reserved.

In recent years, there has been an increasingly heated debate on whether Chinese dark tea is contaminated with mycotoxins and whether it poses health risks to consumers. In this study, a rapid method based on high-performance liquid chromatography was used to detect ochratoxin A (OTA) in Chinese dark tea samples from different regions of China and different years. Of the 228 Chinese dark tea samples tested, 21 were detected for OTA contamination, with a concentration ranging from 2.51 ± 0.16 to 12.62 ± 0.72 μg/kg. Subsequently, a dark tea drinking risk assessment was conducted, and the hazard quotient for each group was far below the acceptable level of 1.0. Of the 12

There is a high mortality rate associated with pancreatic cancer, and the incidence has been rising globally in recent decades. When patients are diagnosed, there is little chance that surgery will be beneficial. Systemic chemotherapy is the currently accepted treatment option for patients with metastatic advanced pancreatic cancer. However, a very limited survival improvement is possible with chemotherapy for advanced pancreatic cancer, and chemotherapy resistance plays a significant role in poor prognosis. Despite the fact that targeting growth factor receptor inhibitors such as anti-vascular endothelial growth factor (VEGFR) antibodies significantly improves survival in pancreatic cancer, only a very small number of patients benefit from the treatment. As emerging drugs, immune checkpoint inhibitors (ICIs) have demonstrated significant therapeutic effects in several tumor types, but monotherapy is not effective in pancreatic cancer. In the first-line treatment of solid tumors, combination therapy may result in remarkable outcomes. Here in, we have reported a younger patient with pancreatic ductal adenocarcinoma with liver metastasis (PDACLM) who had a long-term partial response and good tolerance to the combination of anlotinib and programmed cell death protein 1 (PD-1) inhibitor and chemotherapy. Gene analysis suggested only one mutation in the Kirsten rat sarcoma viral oncogene (KRAS) G12V gene. Consequently, there is some hope for patients with pancreatic cancer, especially for KRAS G12V gene mutated patients. Upon reviewing the literature, this patient’s combination therapy is the first to have been reported.

This work analyzed changes in the corrosion morphology and mechanical performance of 7085 aluminum alloy after outdoor exposures for different times in a humid and hot marine atmospheric environment. After one month of exposure, a pronounced corrosion of the alloy was observed. The corrosion product was mainly Al(OH)3, and the corrosion features were mainly pitting corrosion and intergranular corrosion (IGC). With the exposure time extended from 6 months to 12 months, the IGC depth increased from 114 μm to 190 μm. After a 1-year outdoor exposure in a humid and hot marine environment, the alloy’s ultimate strength and yield stress remained nearly unchanged, while its elongation and area reduction decreased from the original 6% and 9%, respectively, to 3% and 5%. Moreover, the reasons for IGC and its effect on the mechanical performance was analyzed.