Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer.

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism. Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression. Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05). Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

Prevalence and Characteristics of Salmonella from Tibetan Pigs in Tibet, China.

This study aimed to understand the epidemiological characteristics of Salmonella in Tibetan pigs. We isolated, identified, and examined via antimicrobial susceptibility testing on Salmonella from Tibetan pigs breeder farms and slaughterhouses in Tibet, China. A genetic evolutionary tree was constructed on the basis of whole genome sequencing (WGS). A total of 81 Salmonella isolates were isolated from 987 samples. The main serovars were Salmonella Typhimurium and Salmonella London in Tibetan pigs. The isolated Salmonella Typhimurium isolates subjected to antimicrobial susceptibility testing showed varying degrees of resistance to ß-lactams, aminoglycosides, fluoroquinolones, sulfonamides, tetracyclines, and amphenicols. WGS analysis was performed on 20 Salmonella Typhimurium isolates in Tibet (n = 10), Jiangsu (n = 10), and 205 genome sequences downloaded from the Enterobase database to reveal their epidemiological and genetic characteristics. They were divided into two clusters based on core genome single-nucleotide polymorphisms: Cluster A with 112 isolates from Tibet and other regions in China and Cluster B with 113 isolates from Jiangsu and other regions. The isolates in Cluster A were further divided into two subclusters: A-1 with 40 isolates including Tibet and A-2 with 72 isolates from other regions. Virulence factors analysis revealed that all isolates from Tibet carried adeG, but this observation was not as common in Salmonella isolates from Jiangsu and other regions of China. Antibiotic resistance genes (ARGs) analysis showed that all isolates from Tibet carried blaTEM-55 and rmtB, which were absent in Salmonella isolates from Jiangsu and other regions of China. Genetic characteristic analysis and biofilm determination indicated that the biofilm formation capabilities of the isolates from Tibet were stronger than those of the isolates from Jiangsu and other regions of China. Our research revealed the epidemic patterns and genomic characteristics of Salmonella in Tibetan pigs and provided theoretical guidance for the prevention and control of local salmonellosis.

Genome-wide analysis of soybean hypoxia inducible gene domain containing genes: a functional investigation of GmHIGD3.

The response of Hypoxia Inducible Gene Domain (HIGD) proteins to hypoxia plays a crucial role in plant development. However, the research on this gene family in soybean has been lacking. In this study, we aimed to identify and comprehensively analyze soybean HIGD genes using the Glycine max genome database. As a result, six GmHIGD genes were successfully identified, and their phylogeny, gene structures, and putative conserved motifs were analyzed in comparison to Arabidopsis and rice. Collinearity analysis indicated that the HIGD gene family in soybean has expanded to some extent when compared to Arabidopsis. Additionally, the cis-elements in the promoter regions of GmHIGD and the transcription factors potentially binding to these regions were identified. All GmHIGD genes showed specific responsiveness to submergence and hypoxic stresses. Expression profiling through quantitative real-time PCR revealed that these genes were significantly induced by PEG treatment in root tissue. Co-expressed genes of GmHIGD were primarily associated with oxidoreductase and dioxygenase activities, as well as peroxisome function. Notably, one of GmHIGD genes, GmHIGD3 was found to be predominantly localized in mitochondria, and its overexpression in Arabidopsis led to a significantly reduction in catalase activity compared to wild-type plants. These results bring new insights into the functional role of GmHIGD in terms of subcellular localization and the regulation of oxidoreductase activity.

Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPN) share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes (PDAC with cystic changes), which may result in unnecessary surgery. AIM: To investigate the value of computed tomography (CT) in differentiation of SPN from PDAC with cystic changes. METHODS: This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes, confirmed through pathological diagnosis. Quantitative and qualitative analysis was performed, including assessment of age, sex, tumor size, shape, margin, density, enhancement pattern, CT values of tumors, CT contrast enhancement ratios, "floating cloud sign," calcification, main pancreatic duct dilatation, pancreatic atrophy, and peripancreatic invasion or distal metastasis. Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes, and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination. RESULTS: When compared to PDAC with cystic changes, SPN had a lower age (32 years vs 64 years, P < 0.05) and a slightly larger size (5.41 cm vs 3.90 cm, P < 0.05). SPN had a higher frequency of "floating cloud sign" and peripancreatic invasion or distal metastasis than PDAC with cystic changes (both P < 0.05). No significant difference was found with respect to sex, tumor location, shape, margin, density, main pancreatic duct dilatation, calcification, pancreatic atrophy, enhancement pattern, CT values of tumors, or CT contrast enhancement ratios between the two groups (all P > 0.05). The area under the receiver operating characteristic curve of the combination was 0.833 (95% confidence interval: 0.708-0.957) with 78.6% sensitivity, 81.3% specificity, and 80.4% accuracy in differentiation of SPN from PDAC with cystic changes. CONCLUSION: A larger tumor size, "floating cloud sign," and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

Genome-wide identification, structural and gene expression analysis of BTB gene family in soybean.

BACKGROUND: The Bric-a-Brac/Tramtrack/Broad Complex (BTB) gene family plays essential roles in various biological processes in plants. These genes encode proteins that contain a conserved BTB domain, which is involved in protein-protein interactions and regulation of gene expression. However, there is no systematic reports on the BTB gene family in G.max. RESULTS: In total, 122 soybean BTB genes were identified, which were classified into four groups based on the phylogenetic analysis. Gene structures analysis indicated that the number of exon-intron in GmBTBs ranges from 0 to18. Cis-element analysis revealed that most GmBTB genes contained cis-elements related to an abiotic stress response. In addition, qRT-PCR analyses indicated that most GmBTBs are significantly up-regulated under salinity, drought, and nitrate stresses. They suggested their potential for targeted improvement of soybean response to multiple abiotic stresses and nitrate availability. CONCLUSION: These results provide valuable information for identifying the members of the GmBTB gene family in soybean and could provide a functional characterization of GmBTB genes in further research.

Photo-assisted chemical self-rechargeable zinc ion batteries with high charging and discharging efficiency.

Chemically self-recharging zinc ion batteries (ZIBs), which are capable of auto-recharging in ambient air, are promising in self-powered battery systems. Nevertheless, the exclusive reliance on chemical energy from oxygen for ZIBs charging often would bring some obstacles in charging efficiency. Herein, we develop photo-assisted chemically self-recharging aqueous ZIBs with a heterojunction of MoS2/SnO2 cathode, which are favorable to enhancing both the charging and discharging efficiency as well as the chemical self-charging capabilities under illumination. The photo-assisted process promotes the electron transfer from MoS2/SnO2 to oxygen, accelerating the occurrence of the oxidation reaction during chemical self-charging. Furthermore, the electrons within the MoS2/SnO2 cathode exhibit a low transfer impedance under illumination, which is beneficial to reducing the migration barrier of Zn2+ within the cathode and thereby facilitating the uniform inserting of Zn2+ into MoS2/SnO2 cathode during discharging. This photo-assisted chemical self-recharging mechanism enables ZIBs to attain a maximum self-charging potential of 0.95 V within 3 hours, a considerable self-charging capacity of 202.5 mAh g-1 and excellent cycling performance in a self-charging mode. This work not only provides a route for optimizing chemical self-charging energy storage, but also broadens the potential application of aqueous ZIBs.

E3 ubiquitin ligase IPI1 controls rice immunity and flowering via both E3 ligase-dependent and -independent pathways.

Immunity and flowering are energy-consuming processes. However, the mechanism underlying the balance between immunity and flowering remains to be elucidated. Here, we report that the E3 ligase ideal plant architecture 1 interactor 1 (IPI1) controls rice immunity and flowering via two different pathways, one dependent on and another independent of its E3 ligase activity. We found that IPI1, a RING-finger E3 ligase, interacts with another E3 ligase, AvrPiz-t-interacting protein 6 (APIP6), and protects APIP6 from degradation by preventing APIP6's self-ubiquitination. Stabilization of APIP6 by IPI1 requires no IPI1 E3 ligase activity and leads to degradation of APIP6 substrates via the ubiquitin-proteasome system (UPS). Meanwhile, IPI1 directly ubiquitinates OsELF3-1 and OsELF3-2, two homologs of EARLY FLOWERING3 (ELF3), targeting them for degradation via the 26S proteasome. IPI1 knockout plants display early flowering but compromised resistance to rice blast. Thus, IPI1 balances rice immunity and flowering via both E3 ligase-dependent and -independent pathways.

[Effects of Rosa roxburghii Pomace Biochar on Yield and Quality of Chinese Cabbage and Soil Properties].

In order to explore the effect of Rosa roxburghii pomace biochar on the yield and quality of Chinese cabbage and soil properties and realize the resource utilization of R. roxburghii pomace, a pot experiment was conducted to study the effect of R. roxburghii pomace biochar on the yield and quality of Chinese cabbage and soil properties by setting five biochar application rates of 0 % (CK), 1 % (T1), 3 % (T2), 5 % (T3), and 7 % (T4). The results showed that:① The application of R. roxburghii pomace biochar could significantly improve the yield and quality of Chinese cabbage, and the effect was the best at a 5 % biochar application rate. The yield, soluble solids, soluble sugar, vitamin C, total nitrogen, total phosphorus, and total potassium content of Chinese cabbage increased by 71.51 %, 40.14 %, 33.65 %, 38.08 %, 9.03 %, 28.85 %, and 35.38 %, respectively, compared with those in CK. ② The application of biochar from R. roxburghii pomace could significantly improve soil properties and increase soil nutrient content and availability. The effect was better at a 5 % biochar application rate. The soil pH, organic matter, total nitrogen, alkali-hydrolyzable nitrogen, available phosphorus, and available potassium content increased by 41.06 %, 134.84 %, 157.48 %, 140.79 %, 341.75 %, and 627.13 %, respectively, compared with those in CK. The contents of available Fe, Mn, Cu, and Zn and exchangeable Ca and Mg increased by 37.68 %, 61.69 %, 400.00 %, 4 648.84 %, 617.17 %, and 351.42 %, respectively, compared with those in CK. ③ The application of biochar from R. roxburghii pomace could significantly enhance soil enzyme activity. Compared with those in the CK treatment, soil urease, acid phosphatase, catalase, and sucrase increased by 51.43 %-362.86 %, 90.63 %-134.14 %, 21.40 %-85.12 %, and 82.92 %-218.43 %, respectively. ④ Redundancy analysis showed that soil AK; exchangeable Ca, SOM, and AP; and available Zn were the main factors affecting the yield and quality of Chinese cabbage, and there was a significant positive correlation between them. In summary, the application of R. roxburghii pomace biochar can significantly increase the yield and quality of Chinese cabbage and improve soil properties. The preparation of R. roxburghii pomace into biochar can provide a theoretical reference for the rational utilization of R. roxburghii pomace resources.

Prophylactic nicotinamide mononucleotide (NMN) mitigates CSDS-induced depressive-like behaviors in mice via preserving of ATP level in the mPFC.

Depression is a prevalent psychiatric disorder with accumulating evidence implicating dysregulation of extracellular adenosine triphosphate (ATP) levels in the medial prefrontal cortex (mPFC). It remains unclear whether facilitating endogenous ATP production and subsequently increasing extracellular ATP level in the mPFC can exert a prophylactic effect against chronic social defeat stress (CSDS)-induced depressive-like behaviors and enhance stress resilience. Here, we found that nicotinamide mononucleotide (NMN) treatment effectively elevated nicotinamide adenine dinucleotide (NAD+) biosynthesis and extracellular ATP levels in the mPFC. Moreover, both the 2-week intraperitoneal (i.p.) injection and 3-week oral gavage of NMN prior to exposure to CSDS effectively prevented the development of depressive-like behavior in mice. These protective effects were accompanied with the preservation of both NAD+ biosynthesis and extracellular ATP level in the mPFC. Furthermore, catalyzing ATP hydrolysis by mPFC injection of the ATPase apyrase negated the prophylactic effects of NMN on CSDS-induced depressive-like behaviors. Prophylactic NMN treatment also prevented the reduction in GABAergic inhibition and the increase in excitability in mPFC neurons projecting to the lateral habenula (LHb). Collectively, these findings demonstrate that the prophylactic effects of NMN on depressive-like behaviors are mediated by preventing extracellular ATP loss in the mPFC, which highlights the potential of NMN supplementation as a novel approach for protecting and preventing stress-induced depression in susceptible individuals.

Genomic organization and expression profiles of nitrogen assimilation genes in Glycine max.

Background: Glutamine synthetase (GS), glutamate synthase (GOGAT), and nitrate reductase (NR) are key enzymes involved in nitrogen assimilation and metabolism in plants. However, the systematic analysis of these gene families lacked reports in soybean (Glycine max (L.) Merr.), one of the most important crops worldwide. Methods: In this study, we performed genome-wide identification and characterization of GS, GOGAT, and NR genes in soybean under abiotic and nitrogen stress conditions. Results: We identified a total of 10 GS genes, six GOGAT genes, and four NR genes in the soybean genome. Phylogenetic analysis revealed the presence of multiple isoforms for each gene family, indicating their functional diversification. The distribution of these genes on soybean chromosomes was uneven, with segmental duplication events contributing to their expansion. Within the nitrogen assimilation genes (NAGs) group, there was uniformity in the exon-intron structure and the presence of conserved motifs in NAGs. Furthermore, analysis of cis-elements in NAG promoters indicated complex regulation of their expression. RT-qPCR analysis of seven soybean NAGs under various abiotic stresses, including nitrogen deficiency, drought-nitrogen, and salinity, revealed distinct regulatory patterns. Most NAGs exhibited up-regulation under nitrogen stress, while diverse expression patterns were observed under salt and drought-nitrogen stress, indicating their crucial role in nitrogen assimilation and abiotic stress tolerance. These findings offer valuable insights into the genomic organization and expression profiles of GS, GOGAT, and NR genes in soybean under nitrogen and abiotic stress conditions. The results have potential applications in the development of stress-resistant soybean varieties through genetic engineering and breeding.

Quantification and analyses of seven tyrosine kinase inhibitors targeting hepatocellular carcinoma in human plasma by QuEChERS and UPLC-MS/MS.

Tyrosine kinase inhibitors (TKIs) are commonly used to treat various cancers. Literature suggests that the blood concentration of TKIs strongly correlates with their efficacy and adverse effects. Therefore, establishing a Therapeutic Drug Monitoring (TDM) methodology for TKI drugs is crucial to improving their clinical efficacy and minimizing the treatment-related adverse effects. However, quantifying their concentrations in the plasma using existing methods to avoid potential toxicity is challenging. Herein, seven TKIs, namely sorafenib tosylate, axitinib, erlotinib, cediranib, brivanib, linifanib, and golvatinib, were successfully analyzed in human plasma by following a quick, easy, cheap, effective, rugged, and safe (QuEChERS) pretreatment method combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Briefly, biological samples were extracted using 1 mL of methanol, followed by the sequential addition of 250 mg of anhydrous magnesium sulfate and 25 mg of N-propylethylenediamine (PSA) for salinization and purification by adsorption, respectively. In this study, dovitinib was used as the internal standard. The seven TKIs were detected by the gradient elution method for 4 min in the positive ion electrospray mode. The mobile phase comprised methanol (phase A) and 0.1 % aqueous formic acid solution (phase B) on the Agilent Zorbax RRHD Stablebond Aq, (2.1 × 50 mm; 1.8 µm). Brivanib, linifanib, axitinib, sorafenib tosylate, and golvatinib exhibited good linearity in the range of 5-500 ng/mL, and erlotinib and cediranib exhibited good linearity in the range of 10-1000 ng/mL, with linear correlation coefficients (R2) ≥ 0.99. The limits of detection and quantification were 0.60-0.18 ng/mL and 5-10 ng/mL, respectively. The intraday and interday accuracy values ranged from -6.12 % to 7.31 %, with a precision (RSD) of ≤ 10.57 %. The method was rapid, accurate, specific, simple, reproducible, and suitable for the quantitative determination of the seven TKIs in human plasma.

Dual-Ligand Ruthenium Coordination Polymer-Derived Self-Enhanced Electrochemiluminescent Emitters for Sensitive Detection of Procalcitonin.

Ru-based electrochemiluminescence (ECL) coordination polymers are widely employed for bioanalysis and medical diagnosis. However, commonly used Ru-based coordination polymers face the limitation of low efficiency due to the long distance between the ECL reagent and the coreactant dispersed in detecting solution. Herein, we report a dual-ligand self-enhanced ECL coordination polymer, composed of tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)32+) as ECL reactant ligand and ethylenediamine (EDA) as corresponding coreactant ligand into Zn2+ metal node, termed Zn-Ru-EDA. Zn-Ru-EDA shows excellent ECL performance which is attributed to the effective intramolecular electron transport between the two ligands. Furthermore, the dual-ligand polymer allows an anodic low excitation potential (+1.09 V) luminescence. The shift in the energy level of the highest occupied molecular orbital (HOMO) upward after the synthesis of the Zn-Ru-EDA has resulted in a reduced excitation potential. The low excitation potential reduced biomolecular damage and the destruction of the modified electrodes. The ECL biosensor has been constructed using Zn-Ru-EDA with high ECL efficiency for the ultrasensitive detection of a bacterial infection and sepsis biomarker, procalcitonin (PCT), in the range from 1.00 × 10-6 to 1.00 × 10 ng·mL-1 with outstanding selectivity, and the detection limit was as low as 0.47 fg·mL-1. Collectively, the dual-ligand-based self-enhanced polymer may provide an ideal strategy for high ECL efficiency improvement as well as designing new self-enhanced multiple-ligand-based coordination in sensitive biomolecular detection for early disease diagnostics.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Bidentate Coordination Structure Facilitates High-Voltage and High-Utilization Aqueous Zn-I2 Batteries.

The zinc-iodine aqueous battery is a promising energy storage device, but the conventional two-electron reaction potential and energy density of the iodine cathode are far from meeting practical application requirements. Given that iodine is rich in redox reactions, activating the high-valence iodine cathode reaction has become a promising research direction for developing high-voltage zinc-iodine batteries. In this work, by designing a multifunctional electrolyte additive trimethylamine hydrochloride (TAH), a stable high-valence iodine cathode in four-electron-transfer I-/I2/I+ reactions with a high theoretical specific capacity is achieved through a unique amine group, Cl bidentate coordination structure of (TA)ICl. Characterization techniques such as synchrotron radiation, in-situ Raman spectra, and DFT calculations are used to verify the mechanism of the stable bidentate structure. This electrolyte additive stabilizes the zinc anode by promoting the desolvation process and shielding mechanism, enabling the zinc anode to cycle steadily at a maximum areal capacity of 57 mAh cm-2 with 97% zinc utilization rate. Finally, the four-electron-transfer aqueous Zn-I2 full cell achieves 5000 stable cycles at an N/P ratio of 2.5. The unique bidentate coordination structure contributes to the further development of high-valence and high capacity aqueous zinc-iodine batteries.

A systematic review and meta-analysis of Danshen combined with mesalazine for the treatment of ulcerative colitis.

Purpose: Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. Results: A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, p < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Conclusion: Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.

Novel DNA Biosensing Platform for Detecting HIV Integrase for Highly Sensitive and Quantitative HIV Detection, Diagnosis, and Therapeutic Monitoring.

Straightforward, sensitive, and specific human immunodeficiency virus (HIV) assays are urgently needed. The creation of a point-of-care (POC) device for decentralized diagnostics has the potential to significantly reduce the time to treatment, especially for infectious diseases. Notably, however, many POC solutions proposed to date fall short of meeting the ASSURED guidelines, which are crucial for effective deployment in the field. Herein, we developed a DNA biosensor platform for the specific and quantitative detection of HIV. The platform contains a rolling circle amplification (RCA)-based DNA biosensor and a portable fluorescence detector, in which HIV-encoded integrase (IN) enzyme activity is used as a biomarker to achieve HIV-specific detection. The cleavage and integration reaction of IN on the sensor surface and RCA are combined in this detection platform to perform detection signal cascade amplification, ultimately achieving a detection limit of 0.125 CFU/µL of HIV particles. Moreover, the DNA sensor system exhibited high sensitivity and accuracy for detecting HIV in clinical samples, suggesting that it has potential for application in clinical settings to detect retroviruses other than HIV. In addition, quantitative detection based on this biosensing platform was significantly correlated with the CD4+ lymphocytes count, which can provide guidance for antiretroviral therapy and which affects long-term death risk assessment in HIV patients. Therefore, this DNA biosensing platform based on IN activity is expected to be useful for rapid HIV testing, diagnosis, and treatment monitoring, enabling the development of new POC diagnostic tests and will thus be highly valuable for developing HIV prevention strategies and effective treatments.

Memories are One-to-Many Mapping Alleviators in Talking Face Generation.

Talking face generation aims at generating photorealistic video portraits of a target person driven by input audio. According to the nature of audio to lip motions mapping, the same speech content may have different appearances even for the same person at different occasions. Such one-to-many mapping problem brings ambiguity during training and thus causes inferior visual results. Although this one-to-many mapping could be alleviated in part by a two-stage framework (i.e., an audioto- expression model followed by a neural-rendering model), it is still insufficient since the prediction is produced without enough information (e.g., emotions, wrinkles, etc.). In this paper, we propose MemFace to complement the missing information with an implicit memory and an explicit memory that follow the sense of the two stages respectively. More specifically, the implicit memory is employed in the audio-to-expression model to capture high-level semantics in the audio-expression shared space, while the explicit memory is employed in the neural-rendering model to help synthesize pixel-level details. Our experimental results show that our proposed MemFace surpasses all the state-of-theart results across multiple scenarios consistently and significantly.

Cytokines and lymphocyte subsets are associated with disease severity of severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Previous studies have indicated that SFTS patients have a high mortality rate, which may be related to cytokine storm and immune dysfunction. In our study, we analyzed differences in cytokines and lymphocyte subsets between severe and non-severe SFTS patients, with the aim of identifying predictors of severity. METHODS: We retrospectively analyzed demographic characteristics, clinical data, cytokine profiles, and lymphocyte subsets from 96 laboratory confirmed SFTS patients between April 2021 and August 2023. RESULTS: A total of 96 SFTS patients were enrolled, with a mean age of 65.05 (± 7.92) years old. According to our grouping criteria, 35 (36.5%) of these patients were classified as severe group, while 61 (63.5%) were classified as non-severe group. Univariate analysis revealed that age, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-α (IFN-α), CD4 + T cell, and CD8 + T cell counts were risk predictors for the severity of SFTS. Further multivariable logistic regression analysis confirmed age, IL-6 levels, and CD4 + T cell counts as independent predictors of SFTS severity. CONCLUSIONS: Severe SFTS patients may experience cytokine storms and immune dysfunction. Aging, elevated levels of IL-6, and decreased CD4 + T cell count may serve as independent predictors for the severity of SFTS.

The link between gut microbiome and Alzheimer's disease: From the perspective of new revised criteria for diagnosis and staging of Alzheimer's disease.

Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition ("A"), the initial AD pathological feature triggering the "downstream" tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis ("TNIVS"). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome-related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions. HIGHLIGHTS: The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described. Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized. Therapeutic strategies for AD based on the gut microbiome are proposed.