Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis.

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of 'two points of intraneural (endoneural) invasion in the case of four pathological slides' has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.

The role of APOBEC3C in modulating the tumor microenvironment and stemness properties of glioma: evidence from pancancer analysis.

Background: It is now understood that APOBEC3 family proteins (A3s) are essential in tumor progression, yet their involvement in tumor immunity and stemness across diverse cancer types remains poorly understood. Methods: In the present study, comprehensive genome-wide statistical and bioinformatic analyses were conducted to elucidate A3 family expression patterns, establishing clinically relevant correlations with prognosis, the tumor microenvironment(TME), immune infiltration, checkpoint blockade, and stemness across cancers. Different experimental techniques were applied, including RT-qPCR, immunohistochemistry, sphere formation assays, Transwell migration assays, and wound-healing assays, to investigate the impact of A3C on low-grade glioma (LGG) and glioblastoma multiforme (GBM), as well as its function in glioma stem cells(GSCs). Results: Dysregulated expression of A3s was observed in various human cancer tissues. The prognostic value of A3 expression differed across cancer types, with a link to particularly unfavorable outcomes in gliomas. A3s are associated with the the TME and stemness in multiple cancers. Additionally, we developed an independent prognostic model based on A3s expression, which may be an independent prognostic factor for OS in patients with glioma. Subsequent validation underscored a strong association between elevated A3C expression and adverse prognostic outcomes, higher tumor grades, and unfavorable histology in glioma. A potential connection between A3C and glioma progression was established. Notably, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses implicated A3C in immune system-related diseases, with heightened A3C levels contributing to an immunosuppressive tumor microenvironment (TME) in glioma. Furthermore, in vitro experiments substantiated the role of A3C in sustaining and renewing glioma stem cells, as A3C deletion led to diminished proliferation, invasion, and migration of glioma cells. Conclusion: The A3 family exhibits heterogeneous expression across various cancer types, with its expression profile serving as a predictive marker for overall survival in glioma patients. A3C emerges as a regulator of glioma progression, exerting its influence through modulation of the tumor microenvironment and regulation of stemness.

The Safety of CT-Guided Percutaneous Lung Biopsy in Elderly Patients With Solitary Pulmonary Nodules.

OBJECTIVE: Computed tomography (CT)-guided percutaneous lung biopsy is an effective diagnostic procedure for patients with solitary pulmonary nodules (SPN). The aim of this study is to evaluate the safety of this procedure for elderly patients with SPN. METHODS: A total of 125 patients with SPN who received a CT-guided percutaneous lung biopsy were retrospectively analyzed. Patients were divided into elderly (age 65 and above) and non-elderly groups. The patients' characteristics and procedure-related complications were compared between the two groups. RESULTS: The elderly and non-elderly groups included 74 and 51 patients, respectively. The success rate of a CT-guided percutaneous lung biopsy was 100%. The diagnosis rate of lung cancer in the elderly group was significantly higher than that in the non-elderly group (83.78% vs. 64.70%, p = 0.014). The incidence of pulmonary hemorrhage after lung biopsy in the elderly group (44, 59.45%) was significantly higher than that in the non-elderly group (21, 41.17%, p = 0.044), and moderate hemorrhage was the main contributor. The incidence rate of pneumothorax in the elderly group numerically increased, but the difference did not reach statistical significance. CONCLUSION:  Computed tomography-guided percutaneous lung biopsy was an efficient procedure for diagnosing SPN in elderly patients. Although complication rates were relatively higher in elderly patients, the safety of this procedure was acceptable.

Interfacial assembly of chitin/Mn3O4 composite hydrogels as photothermal antibacterial platform for infected wound healing.

To combat bacteria and even biofilm infections, developing alternative antibacterial wound dressings independent of antibiotics is imperative. Herein, this study developed a series of bioactive chitin/Mn3O4 composite hydrogels under mild conditions for infected wound healing application. The in situ synthesized Mn3O4 NPs homogeneously distribute throughout chitin networks and strongly interact with chitin matrix, and as well as endow the chitin/Mn3O4 hydrogels with NIR-assisted outstanding photothermal antibacterial and antibiofilm activities. Meantime, the chitin/Mn3O4 hydrogels exhibit favorable biocompatibility and antioxidant property. Furthermore, the chitin/Mn3O4 hydrogels with the assist of NIR show an excellent skin wound healing performance in a mouse full-thickness S. aureus biofilms-infected wound model, by accelerating the phase transition from inflammation to remodeling. This study broadens the scope for the fabrication of chitin hydrogels with antibacterial property, and offers an excellent alternative for the bacterial-associated wound infection therapy.

CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 µg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

Systemic chemotherapy for unresectable or recurrent primary thymic adenocarcinoma of enteric type.

Primary thymic adenocarcinoma of enteric type is a very rare subtype of thymic carcinoma. Choosing appropriate systemic chemotherapy for patients with unresectable or recurrent disease remain a big challenge. We present a case of 38-year-old man with primary thymic adenocarcinoma of enteric type. The patient received multiline chemotherapy. Metastatic lesions were effectively controlled by FOLFOX (oxaliplatin/5-fluorouracil/leucovorin) chemotherapy. According to the present case and the literature review, FOLFOX and XELOX (capecitabine/oxaliplatin) regimens are reasonable treatment choice for unresectable or recurrent primary thymic adenocarcinoma of enteric type, even in the first-line chemotherapy.

How digitalization and financial development impact eco-efficiency? Evidence from China.

The rapid growth of industrial digitalization and financial support are the main driving forces for the green transformation of China's economy. Aiming to explore how digitalization and financial development impact ecological efficiency (eco-efficiency), this study proposes a unified research framework by integrating multiple technologies using the panel data that covered 30 China's provinces from 2006 to 2018. First, China's provincial digital development index is constructed to measure the level of digitalization, and regional eco-efficiency is estimated by a non-radial data envelope analysis (DEA) model. Based on that, the panel data regression model and panel vector autoregression (PVAR) model are used to explore the direct effects and dynamic effect of digitalization and financial development on eco-efficiency, respectively. Then, the threshold regression model is employed to check the threshold effect of the two variables on eco-efficiency. The following conclusions are drawn: (1) Both digitalization and financial development have a significantly positive correlation with regional eco-efficiency, indicating that China's digitalization and financial development in recent years have both improved regional eco-efficiency. (2) Eco-efficiency has positive and longer responses to the impulse coming from digitalization and financial development, and the response of ecological efficiency to financial development is greater than its response to digitalization. (3) Threshold effects exist in the impact mechanism of digitalization on regional eco-efficiency. This indicates that the level of financial support is too low to promote the improvement in ecological efficiency. Eco-efficiency can be improved only to a certain extent. The research conclusions provide a policy reference for improving eco-efficiency and promoting China's green development.

A novel gut-restricted RIPK1 inhibitor, SZ-15, ameliorates DSS-induced ulcerative colitis.

As a key mediator of cell death and inflammation, receptor-interacting protein kinase 1 (RIPK1) responds to a broad set of inflammatory and pro-death stimuli in human diseases. Inhibitors targeting RIPK1 are being investigated for the treatment of a wide range of human diseases, including ulcerative colitis. In the present study, we designed, synthesized, and investigated the anti-necroptosis and RIPK1-inhibition effects of SZ-15-a symmetrical high-molecular-weight (>500 Da) compound. SZ-15 effectively inhibited necroptosis in U937 and HT-29 cells at concentrations of 1 nM and 10 nM, respectively, and SZ-15 at a concentration of 10 nM almost completely blocked RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) protein phosphorylation induced by necrosis inducers. SZ-15 suppressed the pro-necroptosis function of RIPK1 by downregulating the mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. The activities of SZ-15 were effectively restricted to the gut: The percent recovery of the parent form of SZ-15 in mouse feces was 85.75%. Nevertheless, SZ-15 was effectively absorbed and detected in colon tissues after 1 h at a concentration of 3335 ± 868 ng/g, indicating that membrane permeability was maintained. SZ-15 alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in vivo by decreasing TNF-α, IL-1ß, IL-22, and IL-6 mRNA expression in colonic tissues. Our preclinical study describes a novel gut-restricted RIPK1 inhibitor that shows great potential for use in the clinical treatment of ulcerative colitis.

KC-180-2 Exerts Anti-SCLC Effects via Dual Inhibition of Tubulin Polymerization and Src Signaling.

In this study, a series of N-benzyl-2-(5-phenylpyridin-2-yl) acetamide-based derivatives were successfully designed and synthesized as anti-cancer agents. KC-180-2 was screened as a potentially leading compound with dual mechanisms of action: Src signaling and tubulin polymerization inhibition. It efficiently suppressed the proliferation of five cancer cell lines (MDA-MB-231, H446, SKOV-3, HepG2, and HT29), with IC50 values ranging from 5 to 188 nM, especially small-cell lung cancer (SCLC) cells (IC50, 5 nM). Correspondingly, it exerted a significant therapeutic effect on the H446 small-cell lung cancer xenograft model, significantly reducing the volume of tumors without obvious toxicity. Mechanistically, this compound significantly inhibited the polymerization of purified tubulin in vitro, inducing G2/M cell cycle arrest and binding to the kinase catalytic domain of the Src protein, which reduced the phosphorylation of Src. Thus, KC-180-2 is a potential lead compound for the further development of a new anti-tumor drug against SCLC.

[Value of serum amyloid protein dynamic changes on evaluating condition and prognosis of patients with viral and mycoplasma community-acquired pneumonia].

OBJECTIVE: To investigate the predictive role of dynamic changes of plasma biomarkers in patients with viral and mycoplasma community-acquired pneumonia (CAP). METHODS: From January 2020 to June 2020, 141 patients with viral and mycoplasma CAP in People's Hospital of Ningxia Hui Autonomous Region were enrolled. Pneumonia severity index (PSI) scores [grade I-II (PSI score ≤ 70), grade III (PSI score 71-90) and grade IV-V (PSI score ≥ 91)], serum amyloid A (SAA), hypersensitive C-reactive protein (hs-CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) on the 1 day after admission were compared between the different pathogens (viral and mycoplasma) or different disease severity. The change in level of SAA, hs-CRP on the third day (Δ3 d = 1 d-3 d) were compared among different disease outcome groups (patients were divided into improved group, stable group and exacerbation group based on PSI scores or lung CT images on the third day). The change in the level of SAA, hs-CRP on the seventh day (Δ7 d = 1 d-7 d) were compared among different disease prognosis groups (patients were divided into survival group and death group based on 28-day survival data). The receiver operating characteristic curve (ROC) were drawn to evaluate the value of SAA in the evaluation of disease and prediction prognosis. RESULTS: The level of SAA in mycoplasma group (43 cases) was significantly higher than that in virus group (98 cases) on the 1 day after admission. There were no significant differences in other plasma biomarkers between the two groups. The more severe the illness, the higher the SAA level on the 1 day after admission. The trends of other plasma biomarkers in the two groups were consistent with SAA. The levels of SAA in the patients with exacerbation of the virus group and mycoplasma group (12 cases, 9 cases) were significantly higher than those of the improved group (57 cases, 26 cases) and the stable group (29 cases, 8 cases). SAA increased gradually in the exacerbation group, decreased gradually in the improved group, and slightly increased in the stable group. ΔSAA3 d were differences among three groups. The change trend of hs-CPR was consistent with SAA. The level of SAA in the death group was higher than that in the survival group on the seventh day. SAA increased in the death group and decreased in survival group with time from hospital admission. There were differences according to ΔSAA7 d between death group and survival group. The change trend of hs-CPR was consistent with SAA. ROC curve showed that the value of SAA was better than hs-CRP in assessing the severity of patients on admission day, and the area under ROC curve (AUC) was respectively 0.777 [95% confidence interval (95%CI) was 0.669-0.886], 0.729 (95%CI was 0.628-0.830). The value of ΔSAA3 d was better than SAA on the third day predicting disease trends, and AUC was respectively 0.979 (95%CI was 0.921-1.000), 0.850 (95%CI was 0.660-1.000). hs-CRP on the third day and Δhs-CRP3 d had no predictive value. Both SAA on the seventh day and ΔSAA7 d have predictive value for prognosis. AUC was respectively 0.954 (95%CI was 0.898-0.993) and 0.890 (95%CI was 0.689-1.000). SAA on the seventh day and ΔSAA7 d were better than hs-CRP on the seventh day. Δhs-CRP7 d have no predictive value. CONCLUSIONS: SAA is a sensitive and valuable indicator for CAP patients with viruses and mycoplasma. Dynamic monitoring of SAA can evaluate the patient's progression, prognosis, and assist diagnosis and treatment.

Regioselective Approach to ß-Peroxyl Alcohols and Ethers from Alkenes.

A different regioselective three-component reaction of alkenes, oxygen sources, and hydroperoxides mediated by ammonium iodine to α-oxyperoxidates has been developed. Mechanistic studies demonstrated that regioselective radical addition and subsequent SN2 nucleophilic substitution were possible for the formation of products. In addition to the traditional pathway of SN2 reaction, that is, where nucleophiles attack the α-C atoms at the back side, an additional unusual transition configuration with the H2O molecule attacking the α-C atom at the front side was obtained.

PgtE Enzyme of Salmonella enterica Shares the Similar Biological Roles to Plasminogen Activator (Pla) in Interacting With DEC-205 (CD205), and Enhancing Host Dissemination and Infectivity by Yersinia pestis.

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.

Policy shock effect of SDP on environmental total factors productivity: 53 coal cities versus 165 non-resource-based cities.

The trend of economic decline for coal cities is a serious threat to the high-quality development of China's economy, and how to improve the environmental total factor productivity (ETFP) has become an urgent issue. Based on the framework of data envelopment analysis (DEA), this paper estimates ETFP using the global Malmquist-Luenberger productivity index (GMLPI). We decompose GMLPI into environmental technical efficiency change (ETEC) and the best practice gap change (BPGC). Then, the difference-in-difference (DID) model combining propensity score matching (PSM) method is used to investigate the effect of the Sustainable Development Plan of National Resource-based Cities (2013-2020) (SDP) aiming to improve ETFP. The results indicate that (1) On average, the GMLPI and BPGC are rising, while the ETEC is decreasing in the observed sample period; the western regions have the biggest BPGC, while the eastern regions have the biggest ETEC; (2) The SDP significantly improves the GMLPI and BPGC but has little effect on the ETEC; Coal cities located in eastern and central regions have policy effect, while the western regions do not have. (3) The SDP affects ETFP through slowing down the economic growth rate and reducing population agglomeration, but promoting the optimization of industrial structure. Those findings have policy implications for improving ETFP and promoting the industrial upgrade of coal cities.

Iodine-Initiated Dioxygenation of Aryl Alkenes Using tert-Butylhydroperoxides and Water: A Route to Vicinal Diols and Bisperoxides.

An environment-friendly and efficient dioxygenation of aryl alkenes for the construction of vicinal diols has been developed in water with iodine as the catalyst and tert-butylhydroperoxides (TBHPs) as the oxidant. The protocol was efficient, sustainable, and operationally simple. Detailed mechanistic studies indicated that one of the hydroxyl groups is derived from water and the other one is derived from TBHP. Additionally, the bisperoxides could be obtained in good yields with iodine as the catalyst, Na2CO3 as the additive, and propylene carbonate as the solvent, instead.

Targeting lipid metabolism in multiple myeloma cells: Rational development of a synergistic strategy with proteasome inhibitors.

BACKGROUND AND PURPOSE: Aberrant lipid metabolism is recognized as a key feature of cancer cells. Our initial research on MS-based analysis of lipids in a multiple myeloma (MM) cell line showed a significant accumulation of lipids in multiple myeloma cells after proteasome inhibition. This finding prompted us to hypothesize that multiple myeloma cell survival depends on the maximal utilization of abnormally accumulated lipids. Therefore, we explored whether lipid metabolism-modulating agents would synergize with proteasome inhibitors. EXPERIMENTAL APPROACH: Lipid accumulation in multiple myeloma cells was measured by MS. Synergism between lipid regulators and proteasome inhibitors was assessed by cell viability and apoptosis. A novel stable derivative of fenofibrate (FCE) was synthesized and used to treat multiple myeloma cells in vitro and in vivo along with the proteasome inhibitor ixazomib. ChIP-seq, western blotting and RT-qPCR were performed to explore the potential mechanism(s) underlying the increase in lipid levels in multiple myeloma cells after proteasome inhibition. KEY RESULTS: Accumulation of lipids in multiple myeloma cells was induced by proteasome inhibition. Lipid-lowering drugs and MG-132 exerted a synergistic effect to kill multiple myeloma cells. FCE showed significant synergistic activity in vitro and in vivo with ixazomib. The abnormal lipid accumulation in multiple myeloma cells that was enhanced by proteasome inhibitors might be due to the elevated SREBP1/2 expression induced by ATF4. CONCLUSIONS AND IMPLICATIONS: Our results provide a proof of principle and support for the further clinical evaluation of the combination of lipid-modulating drugs with proteasome inhibitors in the treatment of multiple myeloma.

Case Report: Bilateral Ciliary Body Detachment in a Patient Taking Oral Diet Pills.

SIGNIFICANCE: The use of antiobesity drugs is becoming more widespread, and the resulting adverse effects are also increasing. Visual impairments caused by weight-loss pills need a timely and accurate diagnosis and treatment. Prompt diagnosis and treatment can achieve a satisfactory prognosis. PURPOSE: This report describes a case of a significant decline in bilateral visual acuity caused by taking diet pills and explores the possible pathogenesis. CASE REPORT: A 32-year-old Chinese woman showed shallow anterior chambers, and intraocular pressure (IOP) was 38 mmHg bilaterally after taking Korean prescription diet pills for 6 days. The best-corrected visual acuity of both eyes was 0.03. The ultrasound biomicroscopy showed complete ciliary body detachment accompanied with angle closure. The central anterior chamber depths were 1.70 mm in the right eye and 1.61 mm in the left eye. The patient was diagnosed with ciliary body detachment with secondary elevated IOP. The patient was treated with pilocarpine, carteolol hydrochloride, brinzolamide, mannitol, and dexamethasone sodium phosphate. The patient had rewarding prognosis after treatment with discontinuation of diet pills, control of IOP, and glucocorticoids. CONCLUSIONS: Extensive publicity and education are needed to ensure that consumers do not abuse diet pills; meanwhile, a timely diagnosis and withdrawal are crucial for a desirable prognosis. Clinicians need to consider the possibility of drug-secondary ocular diseases.

Green Fabrication of Chitin/Chitosan Composite Hydrogels and Their Potential Applications.

Chitin is the second most abundant natural polysaccharide with biocompatibility and bioactivity. Aqueous KOH/urea solution is reported for rapid dissolution of chitin, therefore providing a greener and more efficient avenue to fabricate chitin-based functional materials. Chitosan is the most important derivative of chitin with the acetylation degree lower than 60%. Herein, novel chitin/chitosan composite hydrogels are fabricated from the green and highly efficient KOH/urea aqueous system for the first time. Both chitin and chitosan are dissolved in aqueous KOH/urea solutions, then cross-linked by epichlorohydrin to form bulk chitin/chitosan composite hydrogels (CCGEL). The structural, thermal, mechanical, and swelling properties of CCGEL are thoroughly studied. The cell studies show that NIH-3T3 cells self-assemble to form regular 3D multicellular spheroids on the CCGEL samples with high viability. L929 cells proliferate and intend to form cell aggregates, and the size of the cell aggregates becomes greater with the increase of chitosan loading. Additionally, the CCGEL samples exhibit antibacterial activities. Thus, this pioneering work has provided crucial information for novel chitin/chitosan composite materials constructed via the direct dissolution of chitin and chitosan in aqueous KOH/urea solutions, and presented their potential applications in the cell culture and antibacterial fields.

Primary pulmonary lymphoma presenting as nodules and masses: a case report and literature review.

Primary pulmonary lymphoma (PPL) is a rare neoplasm. We report a case of 45-year-old men who was admitted to hospital for multiple nodules and masses in both lungs. The contrast enhanced chest CT scans revealed multiple nodules and masses of varying sizes in right upper and middle lobes and both lower lobes. CT-guided percutaneous transthoracic needle biopsy was performed. The diagnosis of PPL was confirmed by histopathological examination and Immunohistochemical staining. PPL should be included in the differential diagnoses in symptomless patients with multiple pulmonary nodules and masses.

Altered Yersinia pestis virulence is associated with the small regulatory RNA HmsA encoded on the plasmid pPCP1.

Aim: The aim of this study was to access the effect of HmsA, a 65-nt small regulatory RNA encoded by the pPCP1 plasmid, on Yersinia pestis virulence. Materials & methods: Survival and the competition index were determined in mice infected with wild-type Y. pestis and an hmsA deletion mutant. RNA-seq was used to identify HmsA-regulated genes. Results: HmsA deletion enhanced Y. pestis virulence. However, there was no overlap between 18 upregulated genes associated with pathogenicity and potential direct HmsA targets, based on gene expression screening after HmsA-pulse overexpression. Conclusion: HmsA inhibits Y. pestis virulence, but this effect may be mediated by indirect effects on pathogenesis, iron homeostasis and/or other cellular processes.

HOPX Is an Epigenetically Inactivated Tumor Suppressor and Overexpression of HOPX Induce Apoptosis and Cell Cycle Arrest in Breast Cancer.

BACKGROUND: Evidence has been shown that abnormal DNA methylation plays a vital role in the progression of breast cancer via silencing of gene expression. The results of bisulfite sequencing showed that the methylation status of HOPX in breast cancer tissues was higher than that in normal breast cancer tissues, but little known about the biological functions of HOPX in breast cancer. METHODS: A total of 13 paired breast cancer and adjacent noncancerous tissues were subjected to bisulfite sequencing. Meanwhile, the methylation levels of cg218995965 and cg24862548 in breast cancer cells were detected by methylation-specific PCR (MSP). Flow cytometry, wound healing and transwell invasion assays were used to detect the apoptosis, migration and invasion in breast cancer cells. In addition, the expressions of HOPX, p21, cyclin D1 and CDK4 in cells were detected with Western blot assay. RESULTS: Bisulfite sequencing indicated that the CpG sites (cg218995965 and cg24862548) in the HOPX promoter region showed significantly higher methylation in breast cancer tissues. In addition, methylation-specific PCR revealed that HOPX was significantly hypermethylated in breast cancer cell lines MDA-MB-468 and MCF-7. Furthermore, overexpression of HOPX significantly inhibited the proliferation of MDA-MB-468 and MCF-7 cells via inducing the apoptosis. Moreover, upregulation of HOPX markedly inhibited the migration and invasion abilities of MDA-MB-468 cells. Meanwhile, overexpression of HOPX obviously induced cell cycle arrest in MDA-MB-468 cells via upregulation of p21, and downregulation of cyclin D1 and CDK4. Additionally, overexpression of HOPX suppressed tumor growth of breast cancer in vivo. CONCLUSION: Our data showed that HOPX, a tumor suppressor, is epigenetically silenced in breast cancer. Overexpression of HOPX could suppress the progression of breast cancer, and thus indicating that it might serve as a potential target for the treatment of patients with breast cancer.