Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis.

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

Case report: Efficacy of icotinib treatment in lung adenocarcinoma with esophageal squamous cell carcinoma: a rare case of double primary malignant tumors.

Background: Lung adenocarcinoma with esophageal squamous cell carcinoma is rare and the prognosis is poor, therefore there is an urgent need to improve this situation. The objective of this study was to explore the effect of first-generation tyrosine kinase inhibitors (TKIs) in the patient of the double primary malignant tumors. Case report: We report a case of lung adenocarcinoma with esophageal squamous cell carcinoma treated by icotininb after five-year follow-up. A 71-year-old Chinese woman complaining of swallowing obstruction, heartburn, regurgitation of gastric acid for more than 2 months. An esophageal lesion was found by chest CT scans in T7 vertebral level. The diagnosis by gastroscopic biopsy was squamous cell carcinoma (SCC) with EGFR over-expression. Simultaneously, chest CT showed a 2 cm x 1 cm solitary lesion in the right superior pulmonary. The histological diagnosis by percutaneous lung Biopsy was "adenocarcinoma." Epidermal growth factor receptor (EGFR) gene mutation status was evaluated by Sanger sequencing, and an exon 21 point mutation (L858R) was identified. When the double primary malignant tumors were diagnosed, the patient refused operation and received a tyrosine kinase inhibitor (TKI), icotinib, at the dose of 125 mg, three times per day. All serum tumor biomarkers such as CEA and cancer antigen 125 (CA125) were in the normal range during the treatment period. After five-year follow-up, the patient has no evidence of recurrence or metastasis. The lung cancer was stable, meanwhile the esophageal lesion was almost cured. Conclusion: Icotininb is an effective treatment in the patients of the double primary malignant tumors of lung adenocarcinoma with EGFR gene mutation and esophageal squamous cell carcinoma with EGFR over-expression.

Arbuscular mycorrhizal fungi improve growth and tolerance of Platycladus orientalis under lead stress.

Platycladus orientalis is a significant woody plant for phytoremediation in heavy metals contaminated soils. The growth and tolerance of host plants under the lead (Pb) stress were enhanced by arbuscular mycorrhizal fungi (AMF). To evaluate the adjustment by AMF on growth and activity of antioxidant system of P. orientalis under Pb stress. The two-factor pot experiment was conducted with three AM fungal treatments (noninoculated, Rhizophagus irregularis, and Funneliformis mosseae) and four Pb levels (0, 500, 1000, and 2000 mg kg-1). AMF increased dry weight, phosphorus uptake, root vitality, and total chlorophyll content of P. orientalis in spite of Pb stress. Compared with nonmycorrhizal treatments, mycorrhizal P. orientalis had lower H2O2 and malondialdehyde (MDA) contents under Pb stress. AMF increased Pb uptake in roots and decreased the Pb translating to the shoots yet under Pb stress. Total glutathione and ascorbate in roots of P. orientalis were decreased by AMF inoculation. Mycorrhizal P. orientalis had higher superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione S-transferase (GST) activities in shoots and roots than nonmycorrhizal counterparts. Mycorrhizal P. orientalis under Pb stress showed higher expression of PoGST1 and PoGST2 in roots than that in CK treatments. Future studies will explore the function of induced tolerance genes by AMF of P. orientalis under Pb stress.

Arbuscular mycorrhizal fungi (AMF) decreased the reduced toxicity of lead to Platycladus orientalis under lead stress, including improving growth, root activity, photosynthesis, and antioxidant system activity, while reducing its oxidative damage. At the same time, lead inhibited the symbiosis between AMF and Platycladus orientalis.

ZrgA contributes to zinc acquisition in Vibrio parahaemolyticus.

Metals are nutrients essential for almost all lifeforms. Bacteria have evolved several mechanisms to overcome the metal restrictions imposed by the host. Vibrio parahaemolyticus causes severe threats to public health and significant economic losses in shrimp aquaculture. Herein, we report that ZrgA contributes to zinc acquisition in this pathogen. The operon VP_RS01455 to VP_RS01475 of V. parahaemolyticus encodes the putative Zn transporter ZrgABCDE, whose homologs are widely distributed in Vibrionaceae. RNA sequencing analysis revealed that V. parahaemolyticus modulates the transcriptome in response to Zn limitation. Genes in the Zinc uptake regulator (Zur) regulon are upregulated during Zn limitation, including three genes annotated to encode Zn-binding proteins. Significant upregulation of these three genes during Zn limitation was also confirmed by quantitative real-time PCR (qRT-PCR) analysis. However, only the mutants containing a VP_RS01470 (zrgA) deletion exhibited impaired growth under Zn-deficient conditions, indicating that VP_RS01470 plays the predominant role in V. parahaemolyticus Zn acquisition. The VP_RS01470 deletion mutant displayed a false appearance of decreased swimming motility under Zn-deficient conditions, as revealed by the fact that the polar flagellar-related genes were not downregulated in the mutant. Moreover, VP_RS01470 deletion produced no noticeable impact on the swarming motility and virulence in mice. qRT-PCR analysis and ß-galactosidase activity assays indicated that Zur negatively regulates VP_RS01470 expression in V. parahaemolyticus. Collectively, our findings suggest that ZrgA is required for Zn acquisition in V. parahaemolyticus and highlight the importance of detecting the expression of flagellar genes during analysis of motility of a mutant deficient in growth.

BMP2 promotes lung adenocarcinoma metastasis through BMP receptor 2-mediated SMAD1/5 activation.

Bone morphogenetic protein 2 (BMP2) is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. Although several lines of evidence suggest that BMP2 promotes cell migration and invasiveness in vitro, the in vivo role of BMP2 in the metastasis of lung adenocarcinoma cells remains less well understood. Here, we revealed that BMP2 is highly overexpressed in lung adenocarcinoma patients with lymph node metastasis compared with patients without lymph node metastasis. Using an in vivo orthotopic mouse model, we clearly demonstrated that BMP2 promotes lung adenocarcinoma metastasis. The depletion of BMP2 or its receptor BMPR2 significantly reduced cell migration and invasiveness. We further identified that BMP2/BMPR2-mediated cell migration involves the activation of the SMAD1/5/8 signaling pathway, independent of the KRAS signaling pathway. Significantly, the depletion of SMAD1/5/8 or the inhibition of SMAD1/5/8 by LDN193189 inhibitor significantly reduced cell migration. These findings show that BMP2 promotes NSCLC metastasis, indicating that targeting the BMP2 signaling pathway may represent a potential therapeutic strategy for treating patients with metastatic NSCLC.

Toxin-antitoxin systems: Classification, biological roles, and applications.

Toxin-antitoxin (TA) systems, composed of a stable toxin and a cognate unstable antitoxin, are ubiquitous in the genomes of bacteria and archaea. Under suitable growth conditions, an antitoxin prevents its cognate toxin from inducing toxicity; nonetheless, under stress or plasmid loss, it is either rapidly degraded or downregulated, thereby freeing the toxin to exert its activity toward various targets. Currently, TA systems are classified into eight types based on the nature and mode of action of antitoxins. TA expression is tightly regulated at multiple levels. These systems have various biological roles, including genetic element maintenance, virulence, stress resistance, and phage inhibition. Because of the toxic property of toxins, TA systems have been exploited for biotechnological (e.g., DNA cloning, plasmid maintenance, and counterselection) and medical (e.g., antibacterial drugs, antivirals, and anticancer therapies) applications. Herein, we provided an updated overview of TA systems by focusing on their classification, biological roles, and applications. We also described recent advances in research on TA systems and discussed research perspectives in this field.

The AdcR-regulated AdcA and AdcAII contribute additively to zinc acquisition and virulence in Streptococcus suis.

Metals are necessary elements for bacteria. Typically, vertebrate hosts restrict invading bacterial pathogens from accessing metals. Therefore, bacteria have evolved high-affinity metal importers to acquire metals. Streptococcus suis is a major swine pathogen and an emerging zoonotic agent that endangers the swine industry and human health worldwide. Herein, we aimed to identify the zinc acquisition systems in S. suis and evaluate their roles in bacterial virulence. Bioinformatic analyses revealed that S. suis encodes homologues of AdcA and AdcAII, two well-characterised Zn-binding lipoproteins in certain streptococci. Quantitative reverse transcription PCR (qRT-PCR) analysis revealed that the expressions of adcA and adcAII were significantly upregulated in response to Zn limitation, with a higher expression level of adcAII than adcA. Gene deletion mutants and complementation strains were constructed; their growth characteristics under Zn-deficient and Zn-replete conditions indicated that AdcA and AdcAII have overlapping functionality in Zn acquisition. A mouse infection model was used to evaluate the roles of AdcA and AdcAII in S. suis virulence. Mice infected with the double mutant ΔadcAΔadcAII exhibited a significantly higher survival rate, decreased bacterial burden, and lower production of inflammatory cytokines compared to those infected with the wild type (WT) strain. Furthermore, ΔadcAΔadcAII showed reduced competitiveness in infection establishment compared with the WT strain. RNA sequencing, qRT-PCR, and electrophoretic mobility shift assays revealed that AdcR negatively regulates the expressions of adcA and adcAII. Collectively, our results demonstrated that AdcA and AdcAII, which are negatively regulated by AdcR, contribute additively to zinc acquisition and virulence in S. suis.

LbAMT3-1, an ammonium transporter induced by arbuscular mycorrhizal in Lycium barbarum, confers tobacco with higher mycorrhizal levels and nutrient uptake.

KEY MESSAGE: An ammonium transporter LbAMT3-1 overexpression increases the arbuscular abundance of mycorrhizal that opens the possibility of using LbAMT3-1 in breeding programs to improve symbiotic nutrient uptake in Lycium barbarum. Nitrogen (N) is one of the most essential nutrients required by plants and limits net primary production much of the time in most terrestrial ecosystems. Arbuscular mycorrhizal (AM) fungi can enhance plant nutrient uptake and improve plant productivity in nutrient limit ecosystems. Here, we identified an ammonia transporter, LbAMT3-1, specifically induced by AM fungi in Lycium barbarum. To understand the expression characteristics and biological functions, LbAMT3-1 was cloned, characterized, and overexpressed in Nicotiana tabacum (tobacco). A BLAST search identified the coding sequence for LbAMT3-1 with an open-reading frame of 1473 bp. Reverse transcription polymerase chain reaction (RT-PCR) analysis indicated that, besides mycorrhizal roots, LbAMT3-1 were barely detectable in other tissues, including stems and leaves. Promoter-GUS assay showed that GUS staining was detected in mycorrhizal roots, and GUS activity driven by the LbAMT3-1 promoter was exclusively confined to root cells containing arbuscules. LbAMT3-1 functionally complemented the yeast mutant efficiently, and yeast expressing LbAMT3-1 showed well growth on the agar medium with 0.02, 0.2, and 2 mM NH4+ supply. Moreover, overexpression of LbAMT3-1 in N. tabacum resulted a significant increase in arbuscular abundance and enhanced the nutrient acquisition capacity of mycorrhizal plants. Based on the results of our study, we propose that overexpression of LbAMT3-1 can promote P and N uptake of host plants through the mycorrhizal pathway, and increase the colonization intensity and arbuscular abundance, which opens the possibility of using LbAMT3-1 in breeding programs.

Profiling mentally ill offenders in Hong Kong: A 10-year retrospective review study.

INTRODUCTION: This study aimed to analyze the estimated prevalence of mental disorders among offenders and compare the estimated crime rate between mentally ill patients and the total population in Hong Kong. METHODS: Service data of offenders referred to psychiatrists at the Siu Lam Psychiatric Centre from January 2011 to December 2020 were analyzed. Demographic data of gender, age on admission, educational level, principal psychiatric diagnosis, index offense, and assessment outcome were collected. RESULTS: Data of 7535 offenders (74.8% males) aged 14 to 97 (mean: 41.3 ± 13.7) years were analyzed. More than 60% (66.2%) had a diagnosable mental disorder. The most prevalent principal psychiatric diagnosis was schizophrenia and related disorder (22.8%), followed by mental and behavioral disorders due to psychoactive substance use (18.6%), and mood disorders (8.8%). The commonest index offenses were theft and related offenses (20.5%), followed by acts intended to cause injury (19.7%), and illicit drug offenses (11.6%). The estimated prevalence of mental illness among prison population was 7.1% (male: 8.2%, female: 5.0%). The estimated crime rate for mentally ill patients was found to be 43.3 to 263.2 per 100 000 population. DISCUSSION: The estimated prevalence of mental disorders among offenders and the estimated crime rate for mentally ill patients are relatively low in Hong Kong. The result was an important effort to document the changing characteristics of mentally ill offenders and provide an estimation of the prevalence and crime rate for mentally ill patients in Hong Kong.

TroR Negatively Regulates the TroABCD System and Is Required for Resistance to Metal Toxicity and Virulence in Streptococcus suis.

Streptococcus suis is an emerging zoonotic pathogen that causes severe swine and human infections. Metals are essential nutrients for life; however, excess metals are toxic to bacteria. Therefore, maintenance of intracellular metal homeostasis is important for bacterial survival. Here, we characterize a DtxR family metalloregulator, TroR, in S. suis. TroR is located upstream of the troABCD operon, whose expression was found to be significantly downregulated in response to excess manganese (Mn). Deletion of troR resulted in reduced growth when S. suis was cultured in metal-replete medium supplemented with elevated concentrations of zinc (Zn), copper (Cu), or cobalt (Co). Mn supplementation could alleviate the growth defects of the ΔtroR mutant under Zn and Co excess conditions; however, it impaired the growth of the wild-type (WT) and complemented (CΔtroR) strains under Cu excess conditions. The growth of ΔtroR was also inhibited in metal-depleted medium supplemented with elevated concentrations of Mn. Moreover, the ΔtroR mutant accumulated increased levels of intracellular Mn and Co, rather than Zn and Cu. Deletion of troR in S. suis led to significant upregulation of the troABCD operon. Furthermore, troA expression in the WT strain was induced by ferrous iron [Fe(II)] and Co and repressed by Mn and Cu; the repression of troA was mediated by TroR. Finally, TroR is required for S. suis virulence in an intranasal mouse model. Together, these data suggest that TroR is a negative regulator of the TroABCD system and contributes to resistance to metal toxicity and virulence in S. suis. IMPORTANCE Metals are essential nutrients for life; however, the accumulation of excess metals in cells can be toxic to bacteria. In the present study, we identified a metalloregulator, TroR, in Streptococcus suis, which is an emerging zoonotic pathogen. In contrast to the observations in other species that TroR homologs usually contribute to the maintenance of homeostasis of one or two metals, we demonstrated that TroR is required for resistance to the toxicity conferred by multiple metals in S. suis. We also found that deletion of troR resulted in significant upregulation of the troABCD operon, which has been demonstrated to be involved in manganese acquisition in S. suis. Moreover, we demonstrated that TroR is required for the virulence of S. suis in an intranasal mouse model. Collectively, these results suggest that TroR is a negative regulator of the TroABCD system and contributes to resistance to metal toxicity and virulence in S. suis.

A Markerless Gene Deletion System in Streptococcus suis by Using the Copper-Inducible Vibrio parahaemolyticus YoeB Toxin as a Counterselectable Marker.

Streptococcus suis is an important zoonotic pathogen causing severe infections in swine and humans. Induction of the Vibrio parahaemolyticus YoeB toxin in Escherichia coli resulted in cell death, leading to the speculation that YoeBVp can be a counterselectable marker. Herein, the counterselection potential of YoeBVp was assessed in S. suis. The yoeBVp gene was placed under the copper-induced promoter PcopA. The PcopA-yoeBVp construct was cloned into the S. suis-E. coli shuttle vector pSET2 and introduced into S. suis to assess the effect of YoeBVp expression on S. suis growth. Reverse transcription quantitative PCR showed that copper induced yoeBVp expression. Growth curve analyses and spot dilution assays showed that YoeBVp expression inhibited S. suis growth both in liquid media and on agar plates, revealing that YoeBVp has the potential to be a counterselectable marker for S. suis. A SCIY cassette comprising the spectinomycin-resistance gene and copper-induced yoeBVp was constructed. Using the SCIY cassette and peptide-induced competence, a novel two-step markerless gene deletion method was established for S. suis. Moreover, using the ΔperR mutant generated by this method, we demonstrated that PmtA, a ferrous iron and cobalt efflux pump in S. suis, was negatively regulated by the PerR regulator.

Combination and efficiency: preparation of dissolving microneedles array loaded with two active ingredients and its anti-pigmentation effects on guinea pigs.

Hyperpigmentation is a common skin disorder caused by excessive melanogenesis and uneven dispersion of melanin in the skin. To combine multiple active agents with an efficient transdermal drug delivery system is an effective strategy to combat UV induced skin pigmentation. In this work, Arbutin (Arb) and Vitamin C (Vc) mixed in 1:1 were found to have the greatest inhibition effects on melanogenesis and tyrosinase activity in B16 murine melanoma cells. And hyaluronic acid (HA) based dissolving microneedles array (DMNA) was employed to overcome the skin barriers for improved topical drug delivery, which exhibited the most desirable features, including morphology, mechanical properties, dissolving ability, and the highest drug loading. Furthermore, DMNA could greatly increase the stability of Vc during storage without adding any antioxidant which is an important issue for Vc administration. Pharmacodynamics study showed that DMNA loaded with Arb and Vc could synergistically suppress UVB-induced hyperpigmentation in guinea pig skin. This work provides a promising treatment strategy and solution for skin pigmentation and other skin problems.

Genipin induces developmental toxicity through oxidative stress and apoptosis in zebrafish.

Genipin, an iridoid substance, is mainly derived from Gardenia jasminoides Ellis of the traditional Chinese medicine and is widely used in raw materials for the food additive gardenia blue and biological materials. The developmental toxicity of genipin has not been investigated, and its underlying mechanism is unclear. Therefore, in this study we attempt to investigate the potential developmental toxicity of genipin in zebrafish embryos/larvae. The results showed zebrafish embryos treated with 50 µg/ml dose of genipin display inhibited hatching rates and body length. The pericardial edema was observed. It was also found that genipin could induce cardio-toxicity, hepatotoxicity and nephrotoxicity in zebrafish larvae. After genipin treatment, the suppression of antioxidant capacity and increase of oxidative stress were showed for the triggered generation of ROS and MDA, and decreased activity of SOD. Compared with the 0.5% DMSO group, a number of apoptotic cells in zebrafish were increased after genipin exposure. By measuring marker gene expression with the using of qRT-PCR, we proposed that developmental toxicity after genipin treatment might be associated with oxidative stress and apoptosis increase. Our research offers a better understanding for developmental toxicity of genipin.

Roots and stems of Kadsura coccinea extract induced developmental toxicity in zebrafish embryos/larvae through apoptosis and oxidative stress.

CONTEXT: Although the roots and stems of Kadsura coccinea (Lem.) A. C. Smith. [Schisandraceae] are herbs and traditional foods in Li nationality, its toxicity remains unclear. OBJECTIVE: To study developmental toxicity of K. coccinea consumption and explain underlying mechanisms. MATERIALS AND METHODS: Zebrafish were applied to assess LC50 values of hydroethanol extract (KCH) and water extract (KCW) of Kadsura coccinea. In further study, three concentrations groups of KCH (3.75, 7.5 and 15 µg/mL for embryo, 7.5, 15 and 30 µg/mL for larvae) and control group (n = 30) were administered. At specific stages of zebrafish development, spontaneous movement, hatching rate, etc., were measured. Gene expressions related to developmental toxicity were examined. RESULTS: The LC50 value of KCH (24 or 45 µg/mL) was lower than KCW (1447 or 2011 µg/mL) in embryos or larvae. The inhibited spontaneous movement (20%), hatching rate (20%), body length (12%) and eye area (30%) were observed after KCH treatment. Moreover, the decreased liver areas (25%) and fluorescence intensity (33%), increased ALT (37%) and AST levels (42%) were found in larvae treated with KCH (30 µg/mL). The increased ROS (89%), MDA concentrations (30%), apoptosis generation (62%) and decreased T-SOD activity (16%) were also observed. The represented genes of developmental hepatotoxicity, oxidative stress and apoptosis in zebrafish were activated after KCH (15 or 30 µg/mL) treatment. DISCUSSION AND CONCLUSIONS: These results demonstrate that KCH has developmental toxicity on zebrafish. Our study provides a scientific basis for further research on the toxicity of Kadsura coccinea.

Continued gefitinib retreatment beyond progression in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations.

PURPOSE: To evaluate the effectiveness and safety of gefitinib retreatment beyond disease progression in patients with advanced non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations. METHODS: Data from patients with stage III/IV NSCLC were analyzed retrospectively. Patients with sensitive EGFR mutations received first-line treatment with gefitinib followed by retreatment with gefitinib after disease progression. Progression-free survival (PFS) after the first treatment (PFS-1) was defined as the time to progression or death using the Response Evaluation Criteria in Solid Tumors criteria (RECIST) v1.1 criteria. The second PFS (PFS-2) was defined as the interval between the first and second progressions, at the investigator's discretion. Toxicities were recorded in accordance with the National Cancer Institute (NCI)-Common Terminology Criteria (CTC) version 4.0. RESULTS: Sixteen patients aged 53 to 80 years (median 66 years) were included in the analysis. The median PFS-1 and PFS-2 were 10.0 months and 14.0 months, respectively. The median overall survival (OS) was 36.0 months. No toxicity of grade 3 or worse was observed. CONCLUSIONS: Our findings suggest that gefitinib retreatment beyond disease progression may be an effective and tolerable approach for NSCLC patients with sensitive EGFR mutations.

Transcriptomic Analysis of Streptococcus suis in Response to Ferrous Iron and Cobalt Toxicity.

Streptococcus suis is a zoonotic pathogen causing serious infections in swine and humans. Although metals are essential for life, excess amounts of metals are toxic to bacteria. Transcriptome-level data of the mechanisms for resistance to metal toxicity in S. suis are available for no metals other than zinc. Herein, we explored the transcriptome-level changes in S. suis in response to ferrous iron and cobalt toxicity by RNA sequencing. Many genes were differentially expressed in the presence of excess ferrous iron and cobalt. Most genes in response to cobalt toxicity showed the same expression trends as those in response to ferrous iron toxicity. qRT-PCR analysis of the selected genes confirmed the accuracy of RNA sequencing results. Bioinformatic analysis of the differentially expressed genes indicated that ferrous iron and cobalt have similar effects on the cellular processes of S. suis. Ferrous iron treatment resulted in down-regulation of several oxidative stress tolerance-related genes and up-regulation of the genes in an amino acid ABC transporter operon. Expression of several genes in the arginine deiminase system was down-regulated after ferrous iron and cobalt treatment. Collectively, our results suggested that S. suis alters the expression of multiple genes to respond to ferrous iron and cobalt toxicity.

Involvement of Various Enzymes in the Physiology and Pathogenesis of Streptococcus suis.

Streptococcus suis causes severe infections in both swine and humans, making it a serious threat to the swine industry and public health. Insight into the physiology and pathogenesis of S. suis undoubtedly contributes to the control of its infection. During the infection process, a wide variety of virulence factors enable S. suis to colonize, invade, and spread in the host, thus causing localized infections and/or systemic diseases. Enzymes catalyze almost all aspects of metabolism in living organisms. Numerous enzymes have been characterized in extensive detail in S. suis, and have shown to be involved in the pathogenesis and/or physiology of this pathogen. In this review, we describe the progress in the study of some representative enzymes in S. suis, such as ATPases, immunoglobulin-degrading enzymes, and eukaryote-like serine/threonine kinase and phosphatase, and we highlight the important role of various enzymes in the physiology and pathogenesis of this pathogen. The controversies about the current understanding of certain enzymes are also discussed here. Additionally, we provide suggestions about future directions in the study of enzymes in S. suis.

Spin-crossover modulation via single-crystal to single-crystal photochemical [2 + 2] reaction in Hofmann-type frameworks.

This study reports the first modulation of spin-crossover (SCO) behavior via a photochemical [2 + 2] cycloaddition reaction. Here we construct two no-solvent Fe(ii)-Ag(i) bimetallic Hofmann-type frameworks, [Fe(4-spy)2{Ag(CN)2}2] (1) and [Fe(2,4-bpe)2{Ag(CN)2}2] (2) (4-spy = 4-styrylpyridine, 2,4-bpe = trans-1-(2-pyridyl)-2-(4-pyridyl)ethylene). For 1, the dimerization of 4-spy results in a single-crystal to single-crystal (SCSC) transformation from 2D interdigitated layers to a 3D interpenetrated structure. Additionally, a 3D → 3D structural transformation accompanied with Ag(i)-N bond breaking is achieved via the photochemical cycloaddition reaction of 2,4-bpe in 2. More importantly, both the spin transition temperatures and the SCO character are effectively modulated; thus, this approach provides a new strategy for constructing photo-responsive SCO magnetic materials.

Measuring the profiles of the security needs of forensic psychiatric inpatients: Validation of the See, Think, Act Scale.

INTRODUCTION: This study aimed to develop and validate a Chinese version of the See, Think, Act Scale (C-STA). The relational security of the Department of Forensic Psychiatry of Castle Peak Hospital, which provides territory-wide forensic psychiatric services in Hong Kong, was measured. METHODS: The See, Think, Act Scale was first translated into Chinese, then back-translated into English for comparison, and finally, subject to modification until alignment was achieved. Its content validity and face validity were explored through expert panel evaluation and focus group discussion, respectively. Eighty-nine Chinese mental health professionals were recruited from six service units to measure the relational security of the Department of Forensic Psychiatry using the C-STA. RESULTS: The Cronbach's alpha coefficient for internal consistency was high, with all components exceeding 0.90. The intraclass correlation coefficients for the test-retest reliability of all components ranged from 0.50 to 0.72. Participants had the lowest score on the "patient focus" component (M = 2.56, standard deviation [SD] = 0.32). A significant sex difference in total relational security scores was found (P < 0.001). DISCUSSION: The C-STA is a valid and reliable instrument to measure the relational security of forensic psychiatric services. "Patient focus" might be the target component of relational security for which the Department of Forensic Psychiatry needs to have interventions. The significant sex difference in total relational security scores needs further exploration.

Down-regulation of miR-205-5p sensitizes HNE1/DDP to cisplatin induced apoptosis in vitro / 药学学报

This study aims to investigate the effect of down-regulation of miR-205-5p by transfection of miR-205-5p inhibitor on the sensitivity of HNE1/DDP cells to cisplatin (DDP) induced apoptosis and explore the underlying mechanism. qRT-PCR was used to detect the expression of miR-205-5p in HNE1 or HNE1/DDP cells. The expression level of miR-205-5p was analyzed after transfecting HNE1/DDP cells with miR-205-5p inhibitor. MTT assay was used to evaluate the inhibitory effect of DDP alone or in combination with miR-205-5p inhibitor on the proliferation of HNE1/DDP or HNE1 cells. Apoptosis of cells treated with miR-205-5p inhibitor alone or in combination with DDP (8 μmol·L-1) was assessed using flow cytometry with PI staining, with the nucleus was counterstained with DAPI staining. The expression of Bax, Bak, Mcl-1, or Bcl-2 was analyzed by Western blot. HNE1/DDP cells showed a high level of expression of miR-205-5p, and the expression of miR-205-5p was significantly decreased by transfection of miR-205-5p inhibitor. Down-regulation of miR-205-5p significantly increased the sensitivity of HNE1/DDP cells to DDP (P<0.05). Transfection of miR-205-5p inhibitor enhanced the sensitivity of HNE1/DDP cells to DDP induced apoptosis. Treatment of HNE1/DDP cells with miR-205-5p inhibitor combined with DDP (8 μmol·L-1) for 24 h resulted in an apoptotic rate of 28.93% ± 2.50%, significantly higher than that treated with miR-205-5p inhibitor (9.83% ± 1.31%) or DDP alone (10.83% ± 1.70%) (P<0.05). DAPI staining showed that HNE1/DDP cell nucleus became significantly condensed and fragmented in miR-205-5p inhibitor combined with DDP group. The combined group up-regulated the expression of Bax and down-regulated the expression of Bcl-2 in HNE1/DDP cells. Therefore, down-regulation of miR-205-5p can enhance the sensitivity of HNE1/DDP cells to cisplatin induced apoptosis, and the mechanism may involve up-regulation of Bax and down-regulation of Bcl-2 expression.