Impact of Treatment Response on Risk of Serious Infections in Patients With Crohn's Disease: Secondary Analysis of the PYRAMID Registry.

BACKGROUND & AIMS: Traditional risk factors for serious infections with advanced therapies in patients with Crohn's disease (CD) have been assessed at baseline before starting therapy. We evaluated the impact of treatment response on the risk of serious infections in adalimumab-treated patients with CD through secondary analysis of the PYRAMID registry (NCT00524537). METHODS: We included patients with CD who initiated adalimumab and classified them as treatment responders (achieved steroid-free clinical remission based on patient-reported outcomes) vs nonresponders (not in steroid-free clinical remission) at 6 months after treatment initiation (landmark). We compared the risk of serious infections between responders vs nonresponders between 6 and 36 months after treatment initiation through stabilized inverse probability of treatment weighting Cox proportional hazards model. RESULTS: Of 1515 adalimumab-treated patients, 763 (50.4%) were classified as responders at 6 months (37 ± 13 y; 56% female; disease duration, 9.5 ± 8.5 y). Compared with nonresponders, responders were less likely to have moderate to severe symptoms (55.6% vs 33%), or require steroids (45.5% vs 17.3%) or opiates (6.6% vs 1.3%) at baseline, without any differences in disease location, perianal disease, and prior CD complications. During follow-up evaluation, using stabilized inverse probability of treatment weighting, responders were 34% less likely to experience serious infections compared with nonresponders (hazard ratio, 0.66; 95% CI, 0.46-0.96). Risk of gastrointestinal and extraintestinal infections was lower in responders vs nonresponders. CONCLUSIONS: Patients with CD who respond to adalimumab have a lower risk of developing serious infections compared with nonresponders. These findings underscore that initiation of advanced therapy for CD may lower the risk of serious infections through effective disease control and avoidance of corticosteroids.

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths among cancer patients. Vascular endothelial growth factor A (VEGFA) is involved in regulating biological processes, such as angiogenesis and vascular permeability, and is very closely related to the pathogenesis of various tumours, especially vascular-rich, solid tumours. Clinical data of patients with HCC and other tumours were analysed through public databases, such as the TCGA database, Gene Expression Omnibus database, Human Protein Atlas database, STRING, Tumour Immune Estimation Resource and Kaplan-Meier Plotter. The tumour tissues and adjacent normal tissues of patients with HCC from Hunan Provincial People's Hospital were collected to verify the expression of VEGFA by immunohistochemistry, immunofluorescence, Western blotting and qPCR. VEGFA expression is elevated in multiple tumour types and correlates with the prognosis of tumour patients. VEGFA is involved in regulating the tumour microenvironment and immune cell function in tumour development. Inhibition of VEGFA reduces proliferation, invasion, and migration and promotes apoptosis in HCC cells. VEGFA is a potential predictive biomarker for the diagnosis and prognosis of HCC.

S100A family is a group of immune markers associated with poor prognosis and immune cell infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common human cancers with poor prognosis in the world. HCC has become the second leading cause of cancer-related death in China. It is urgent to identify novel biomarker and valid target to effectively diagnose, treat or predict the prognosis of HCC. It has been reported that S100A family is closely related to cell proliferation and migration of different cancers. However, the values of S100As in HCC remain to be further analyzed. METHODS: We investigated the transcriptional and translational expression of S100As, as well as the value of this family in HCC patients from the various databases. RESULTS: S100A10 was most relevant to HCC. CONCLUSIONS: The results from HCC patients' tissues and different cells also confirmed the role of S100A10 in HCC. Furthermore, we proved that S100A10 could influenced the cell proliferation of HCC cells via ANXA2/Akt/mTOR pathway. However, it would appear that the relationship between S100A10 and HCC is complex and requires more research.

Promoting genotype-independent plant transformation by manipulating developmental regulatory genes and/or using nanoparticles.

KEY MESSAGE: This review summarizes the molecular basis and emerging applications of developmental regulatory genes and nanoparticles in plant transformation and discusses strategies to overcome the obstacles of genotype dependency in plant transformation. Plant transformation is an important tool for plant research and biotechnology-based crop breeding. However, Plant transformation and regeneration are highly dependent on species and genotype. Plant regeneration is a process of generating a complete individual plant from a single somatic cell, which involves somatic embryogenesis, root and shoot organogeneses. Over the past 40 years, significant advances have been made in understanding molecular mechanisms of embryogenesis and organogenesis, revealing many developmental regulatory genes critical for plant regeneration. Recent studies showed that manipulating some developmental regulatory genes promotes the genotype-independent transformation of several plant species. Besides, nanoparticles penetrate plant cell wall without external forces and protect cargoes from degradation, making them promising materials for exogenous biomolecule delivery. In addition, manipulation of developmental regulatory genes or application of nanoparticles could also bypass the tissue culture process, paving the way for efficient plant transformation. Applications of developmental regulatory genes and nanoparticles are emerging in the genetic transformation of different plant species. In this article, we review the molecular basis and applications of developmental regulatory genes and nanoparticles in plant transformation and discuss how to further promote genotype-independent plant transformation.

Genetic background and cis-organization regulate ALDH7B4 gene expression in Eutrema salsugineum: a promoter analysis case study.

MAIN CONCLUSION: ALDH7B4 promoter analysis in A. thaliana and E. salsugineum reveals that both genetic background and promoter architecture contribute to gene expression in response to stress in different species. Many genes are differentially regulated in a comparison of salinity-sensitive and salinity-tolerant plant species. The aldehyde dehydrogenase 7B4 (ALDH7B4) gene is turgor-responsive in A. thaliana and encodes a highly conserved detoxification enzyme in plants. This study compared the ALDH7B4 gene in A. thaliana (salinity-sensitive) and in the salinity-tolerant close relative Eutrema salsugineum. EsALDH7B4 in E. salsugineum is the ortholog of AtALDH7B4 and the expression is also salinity, drought, and wound responsive. However, E. salsugineum requires higher salinity stress to induce the EsALDH7B4 transcriptional response. The GUS expression driven either by the promoter AtALDH7B4 or EsALDH7B4 was induced under 300 mM NaCl treatment in A. thaliana while 600 mM NaCl treatment was required in E. salsugineum, suggesting that the genetic background plays a crucial role in regulation of gene expression. Promoter sequences of ALDH7B4 are less conserved than the protein coding region. A series of EsALDH7B4 promoter deletion fragments were fused to the GUS reporter gene and promoter activity was determined in A. thaliana. The promoter region that contains two conserved ACGT-containing motifs was identified to be essential for stress induction. Furthermore, a 38 bp "TC" rich motif in the EsALDH7B4 promoter, absent from the AtALDH7B4 promoter, negatively affects EsALDH7B4 expression. A MYB-like transcription factor was identified to bind the "TC" motif and to repress the EsALDH7B4 promoter activity. This study reveals that genetic background and cis-acting elements coordinately regulate gene expression.

Epigenetic Dynamics and Regulation of Plant Male Reproduction.

Flowering plant male germlines develop within anthers and undergo epigenetic reprogramming with dynamic changes in DNA methylation, chromatin modifications, and small RNAs. Profiling the epigenetic status using different technologies has substantially accumulated information on specific types of cells at different stages of male reproduction. Many epigenetically related genes involved in plant gametophyte development have been identified, and the mutation of these genes often leads to male sterility. Here, we review the recent progress on dynamic epigenetic changes during pollen mother cell differentiation, microsporogenesis, microgametogenesis, and tapetal cell development. The reported epigenetic variations between male fertile and sterile lines are summarized. We also summarize the epigenetic regulation-associated male sterility genes and discuss how epigenetic mechanisms in plant male reproduction can be further revealed.

Quantifying the Impact of COVID-19 Nonpharmaceutical Interventions on Influenza Transmission in the United States.

BACKGROUND: Nonpharmaceutical interventions (NPIs) have been implemented to suppress transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence indicates that NPIs against coronavirus disease 2019 (COVID-19) may also have effects on transmission of seasonal influenza. METHODS: In this study, we use an absolute humidity-driven susceptible-infectious-recovered-susceptible (SIRS) model to quantify the reduction of influenza incidence and transmission in the United States and US Department of Health and Human Services regions after implementation of NPIs in 2020. We investigate long-term effect of NPIs on influenza incidence by projecting influenza transmission at the national scale over the next 5 years, using the SIRS model. RESULTS: We estimate that incidence of influenza A/H1 and B, which circulated in early 2020, was reduced by more than 60% in the United States during the first 10 weeks following implementation of NPIs. The reduction of influenza transmission exhibits clear geographical variation. After the control measures are relaxed, potential accumulation of susceptibility to influenza infection may lead to a large outbreak, the scale of which may be affected by length of the intervention period and duration of immunity to influenza. CONCLUSIONS: Healthcare systems need to prepare for potential influenza patient surges and advocate vaccination and continued precautions.

Low-dose X-ray enhanced tumor accumulation of theranostic nanoparticles for high-performance bimodal imaging-guided photothermal therapy.

BACKGROUND: Theranostic nanoparticles (NPs) have achieved rapid development owing to their capacity for personalized multimodal diagnostic imaging and antitumor therapy. However, the efficient delivery and bulk accumulation of NPs in tumors are still the decisive factors in improving therapeutic effect. It is urgent to seek other methods to alters tumor microenvironment (like vascular permeability and density) for enhancing the efficiency of nanoparticles delivery and accumulation at the tumor site. METHODS: Herein, we developed a Raman-tagged hollow gold nanoparticle (termed as HAuNP@DTTC) with surface-enhanced Raman scattering (SERS) property, which could be accumulated efficiently in tumor site with the pre-irradiation of low-dose (3 Gy) X-ray and then exerted highly antitumor effect in breast cancer model. RESULTS: The tumor growth inhibition (TGI) of HAuNP@DTTC-induced photothermal therapy (PTT) was increased from 60% for PTT only to 97%, and the lethal distant metastasis of 4T1 breast cancer (such as lung and liver) were effectively inhibited under the X-ray-assisted PTT treatment. Moreover, with the strong absorbance induced by localized surface plasmon resonance in near-infrared (NIR) region, the signals of Raman/photoacoustic (PA) imaging in tumor was also significantly enhanced after the administration of HAuNP@DTTC, indicating it could be used as the Raman/PA imaging and photothermal agent simultaneously under 808 nm laser irradiation. CONCLUSIONS: Our studied of the as-prepared HAuNP@DTTC integrated the Raman/PA imaging and PTT functions into the single platform, and showed the good prospects for clinical applications especially with the low-dose X-ray irradiation as an adjuvant, which will be a productive strategy for enhancing drug delivery and accumulation in tumor theranostics.

Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer.

BACKGROUND: Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy. METHODS: Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer. RESULTS: Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model. CONCLUSIONS: We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.

An ultrasensitive, homogeneous fluorescence quenching immunoassay integrating separation and detection of aflatoxin M1 based on magnetic graphene composites.

A homogeneous fluorescence quenching immunoassay is described for simultaneous separation and detection of aflatoxin M1 (AFM1) in milk. The novel assay relies on monoclonal antibody (mAb) functionalized Fe3O4 decorated reduced-graphene oxide (rGO-Fe3O4-mAb) as both capture probe and energy acceptor, combined with tetramethylrhodamine cadaverine-labeled aflatoxin B1 (AFB1-TRCA) as the energy donor. In the assay, AFB1-TRCA binds to rGO-Fe3O4-mAb in the absence of AFM1, quenching the fluorescence of TRCA by resonance energy transfer. Significantly, the immunoassay integrates sample preparation and detection into a single step, by using magnetic graphene composites to avoid washing and centrifugation steps, and the assay can be completed within 10 min. Under optimized conditions, the visual and quantitative detection limits of the assay for AFM1 were 50 and 3.8 ng L-1, respectively, which were significantly lower than those obtained by fluorescence polarization immunoassay using the same immunoreagents. Owing to its operation and highly sensitivity, the proposed assay provides a powerful tool for the detection of AFM1.

H2 S-Scavenged and Activated Iron Oxide-Hydroxide Nanospindles for MRI-Guided Photothermal Therapy and Ferroptosis in Colon Cancer.

Overproduced hydrogen sulfide (H2 S) is of vital importance for the progress of colon cancer and promotes cancer cellular proliferation. Devising pharmacological nanomaterials for tumor-specific H2 S activation will be significant for precise colon cancer treatment. Herein, a biocompatible fusiform iron oxide-hydroxide nanospindles (FeOOH NSs) nanosystem for magnetic resonance imaging (MRI), ferroptosis, and H2 S based cascade reaction-enhanced combinational colon cancer treatment is developed. The FeOOH NSs can effectively scavenge endogenous H2 S via the reduction reaction to prohibit the growth of CT26 colon cancer. The cascade produced FeS driven by overexpressed H2 S exhibits near-infrared-triggered photothermal therapy capability and Fe2+ -mediated ferroptosis functionality. Meanwhile, the as-prepared FeOOH NSs can light up tumor tissues as a potent MRI contrast agent. Additionally, FeOOH NSs present desirable biosafety in a murine model for up to three months and avoid any long-term toxicity. Furthermore, it is found that these H2 S-responsible nanotheranostics do not cause any cure effects on other cancer types, such as 4T1 breast cancer. Overall, the findings illustrate that the biocompatible FeOOH NSs can be successfully employed as a theranostic for specifically treating colon cancer, which may promote the clinical translation and development of H2 S-responsive nanoplatforms.

Ultrasound-enhanced nano catalyst with ferroptosis-apoptosis combined anticancer strategy for metastatic uveal melanoma.

Uveal melanoma is the most common primary ocular tumor owing to its highly invasive and metastatic characteristics. Currently, standard clinical treatment has an unsatisfied curative effect due to the lack of an effective approach to inhibit the tumor metastasis. Therefore, it is necessary to develop a new strategy that can both restraint local tumors and suppress the ocular tumor metastasis. Herein, we developed ultrasound-responsive nanoparticles (FeP NPs) that can both hinder the growth of in situ ocular tumor and prevent the tumor metastasis through the ferroptosis-apoptosis combined-anticancer strategy. The FeP NPs were assembling by stimulating gallic acid-Fe (III) and paclitaxel, then could be internalized into tumor cells under the cooperative effect of ultrasound, which further activates the intracellular Fenton reaction and generates high reactive oxygen species levels, ultimately leading to mitochondrial damage, lipid per-oxidation, and apoptosis. The FeP NPs can efficiently inhibit the tumor growth in an orthotopic uveal melanoma model. More importantly, the level of the promoting-metastatic factor nerve growth factor receptor (NGFR) secreted by cancer cells is significantly reduced, further limits cancer metastasis to the cervical lymph node and finally inhibits lung metastasis of uveal melanoma. We believe that these designed ultrasound-enhanced nanoparticles possess potential clinical application for preventing the regeneration and metastasis of uveal melanoma.

Salivary CD44 and Total Protein Levels to Detect Risk for Oral and Oropharyngeal Cancer Recurrence: A Nonrandomized Clinical Trial.

Importance: Oral and oropharyngeal cancer have low survival rates, and incidence continues to increase. Objective: To determine whether soluble CD44 and total protein (TP) are useful for monitoring head and neck cancer recurrence, either used in a point-of-care (POC) test or as individual laboratory-based biomarkers. Design, Setting, and Participants: This multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay took place across the University of California, San Diego; Johns Hopkins University; the Greater Baltimore Medical Center; New York University; and the San Diego Veterans Affairs Hospital. Patients with newly biopsy-proven, untreated oral cavity and oropharyngeal cancer were enrolled. Patients were enrolled April 2017 to April 2019, and data were analyzed December 2022 to June 2023. Exposure: POC salivary oral rinse test. Main Outcomes and Measures: Oral rinses were collected at pretreatment baseline and 3, 6, 12, and 18 months after completion of therapy; participants were then followed up for 3 years to define disease status. Associations of baseline characteristics with a positive test were evaluated by Fisher exact test. The association of a positive value on the CD44 or TP test with progression-free survival was evaluated in an adjusted multivariable proportional hazards model. Results: Of 172 patients enrolled, the mean (SD) age was 62.5 (10.2) years, and 122 (70.9%) identified as male. Additionally, 92 patients (53.3%) had never smoked, 99 (57.6%) formerly or currently drank alcohol, and 113 (65.7%) presented with oropharyngeal cancers, which were positive for human papillomavirus in 95 (84.1%). Tumor site was associated with test results at baseline; patients with oral cavity cancer had a higher baseline positive POC test rate (47 of 51 [92.2%]) compared to patients with oropharyngeal cancer (85 of 110 [77.3%]). Using Cox regression models with CD44 or TP level as a time-varying covariate, a higher CD44 level showed a statistically significant association with a higher hazard of recurrence (hazard ratio, 1.06; 95% CI, 1.00-1.12), though the TP level was not statistically significant. In multivariate adjusted analysis, higher CD44 and TP levels were associated with increased hazard ratios of recurrence of 1.13 (95% CI, 1.04-1.22) and 3.51 (95% CI, 1.24-9.98), respectively. Conclusion and Relevance: In this multi-institutional nonrandomized clinical trial of an assay, posttreatment longitudinal monitoring for elevated salivary CD44 and TP levels using an enzyme-linked immunosorbent assay-based laboratory test identified patients at increased risk of future cancer recurrence. The CD44 and TP rapid POC test holds some promise, but further development is needed for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT03148665.

Designing Fast-Moving Antibacterial Microtorpedoes to Treat Lethal Bacterial Biofilm Infections.

Engineering fast-moving microrobot swarms that can physically disassemble bacterial biofilms and kill the bacteria released from the biofilms is a promising way to combat bacterial biofilm infections. Here, we report electrochemical design of Ag7O8NO3 microtorpedoes with outstanding antibacterial performance and meanwhile capable of moving at speeds of hundreds of body lengths per second in clinically used H2O2 aqueous solutions. These fast-moving antibacterial Ag7O8NO3 microtorpedoes could penetrate into and disintegrate the bacterial biofilms and, in turn, kill the bacteria released from the biofilms. Based on the understanding of the growth behavior of the microtorpedoes, we could fine-tune the morphology of the microtorpedoes to accelerate the moving speed and increase their penetration depth into the biofilms simply via controlling the potential waveforms. We further developed an automatic shaking method to selectively peel off the uniformly structured microtorpedoes from the electrode surface, realizing continuous electrochemical production of the microtorpedoes. Animal experiments proved that the microtorpedo swarms greatly increased the survival rate of the mice infected by lethal biofilms to >90%. We used the electrochemical method to design and massively produce uniformly structured fast-moving antibacterial microtorpedo swarms with application potentials in treatment of lethal bacterial biofilm infections.

Enzyme-free and rapid colorimetric analysis of osteopontin via triple-helix aptamer probe coupled with catalytic hairpin assembly reaction.

BACKGROUND: Osteopontin (OPN) is closely associated with tumorigenesis, growth, invasion, and immune escape and it serves as a plasma biomarker for hepatocellular carcinoma (HCC). Nevertheless, the accurate and rapid detection of low-abundance OPN still poses significant challenges. Currently, the majority of protein detection methods rely heavily on large precision instruments or involve complex procedures. Therefore, developing a simple, enzyme-free, rapid colorimetric analysis method with high sensitivity is imperative. RESULTS: In this study, we have developed a portable colorimetric biosensor by integrating the triple-helix aptamer probe (THAP) and catalytic hairpin assembly (CHA) strategy, named as T-CHA. After binding to the OPN, the trigger probe can be released from THAP, then initiates the CHA reaction and outputs the signal through the formation of a G-quadruplex/Hemin DNAzyme with horseradish peroxidase-like activity. Consequently, this colorimetric sensor achieves visual free-labeled detection without additional fluorophore modification and allows for accurate quantification by measuring the optical density of the solution at 650 nm. Under optimal conditions, the logarithmic values of various OPN concentrations exhibit satisfactory linearity in the range of 5 pg mL-1 to 5 ng mL-1, with a detection limit of 2.04 pg mL-1. Compared with the widely used ELISA strategy, the proposed T-CHA strategy is rapid (∼105 min), highly sensitive, and cost-effective. SIGNIFICANCE: The T-CHA strategy, leveraging the low background leakage of THAP and the high catalytic efficiency of CHA, has been successfully applied to the detection of OPN in plasma, demonstrating significant promise for the early diagnosis of HCC in point-of-care testing. Given the programmability of DNA and the universality of T-CHA, it can be readily modified for analyzing other useful tumor biomarkers.

Gestational psittacosis causes severe pneumonia and miscarriage: A case report and literature review.

Psittacosis is an uncommon zoonotic illness, and gestational psittacosis is even rarer. The clinical signs and symptoms of psittacosis are varied, often overlooked, and swiftly identified by metagenomic next-generation sequencing. We recorded the case of a 41-year-old pregnant woman with psittacosis where the disease was not detected early on, resulting in severe pneumonia and fetal miscarriage. The clinical symptoms, diagnosis, and treatment of psittacosis in pregnancy are the subject of this case study.

Structural and molecular basis of pollen germination.

Pollen germination is a prerequisite for double fertilization of flowering plants. A comprehensive understanding of the structural and molecular basis of pollen germination holds great potential for crop yield improvement. The pollen aperture serves as the foundation for most plant pollen germination and pollen aperture formation involves the establishment of cellular polarity, the formation of distinct membrane domains, and the precise deposition of extracellular substances. Successful pollen germination requires precise material exchange and signal transduction between the pollen grain and the stigma. Recent cytological and mutant analysis of pollen germination process in Arabidopsis and rice has expanded our understanding of this biological process. However, the overall changes in germination site structure and energy-related metabolites during pollen germination remain to be further explored. This review summarizes and compares the recent advances in the processes of pollen aperture formation, pollen adhesion, hydration, and germination between eudicot Arabidopsis and monocot rice, and provides insights into the structural basis and molecular mechanisms underlying pollen germination process.

Decompression Mechanism of Radish Seed in Prehypertension Rats through Integration of Transcriptomics and Metabolomics Methods.

Radish seed (RS), the dried ripe seed of Raphanus sativus L., is widely used in traditional Chinese medicine (TCM) to reduce blood pressure. However, the molecular and pharmacological mechanisms underlying its therapeutic effects are still unclear. In this study, we analyzed the effects of RS in a rat model of prehypertension and assessed the mechanistic basis by integrating transcriptomics and metabolomics. RS administration significantly reduced blood pressure in prehypertensive male Wistar rats, negatively regulated endothelin-1, increased nitric oxide levels, and reduced the exfoliation of endothelium cells. In vitro vascular ring experiments further confirmed the effects of RS on vascular endothelial cells. Furthermore, we identified 65 differentially expressed genes (DEGs; P adj < 0.05 and fold change (FC) > 2) and 52 metabolites (VIP > 1, P < 0.05 and FC ≥ 2 or ≤0.5) in the RS intervention group using RNA-seq and UPLC-MS/MS, respectively. A network of the DEGs and the metabolites was constructed,q which indicated that RS regulates purine metabolism, linoleic acid metabolism, arachidonic acid metabolism, circadian rhythm, and phosphatidylinositol signaling pathway, and its target genes are Pik3c2a, Hspa8, Dnaja1, Arntl, Ugt1a1, Dbp, Rasd1, and Aldh1a3. Thus, the antihypertensive effects of RS can be attributed to its ability to improve vascular endothelial dysfunction by targeting multiple genes and pathways. Our findings provide new insights into the pathological mechanisms underlying prehypertension, along with novel targets for the prevention and treatment of hypertension.

Biocompatible Gallium Nanodots against Drug-Resistant Bacterial Pneumonia and Liver Abscess.

Resistant bacterial infection remains a severe public health threat, and conventional antibiotic drugs work poorly in effectively treating infectious diseases. Here, we developed gallium-based nanodots (Ga NDs), consisting of specific disruption of bacterial iron ability, to treat multidrug-resistant (MDR) Gram-negative bacteria-infected diseases. The Ga NDs significantly suppress the proliferation of two typical MDR bacteria strains (P. aeruginosa and ESBL E. coli) compared with clinically used antibacterial drugs, including penicillin and levofloxacin. Ga NDs could also disrupt the biofilms of these two bacterial strains. In P. aeruginosa infected pneumonia and ESBL E. coli infected acute liver abscess models, the Ga NDs enable substantial inhibition of bacterial growth and reduce the organs' inflammation that resulted in significant improvement of survival. Further, the Ga NDs demonstrated excellent biocompatibility and biosafety characteristics. Together, we believe that our gallium containing nanotherapeutics are expected to be developed into promising alternative therapies to combat drug-resistant bacterial infection.