Metabolic engineering of Escherichia coli for the production of an antifouling agent zosteric acid.

Zosteric acid (ZA) is a Zostera species-derived, sulfated phenolic acid compound with antifouling activity and has gained much attention due to its nontoxic and biodegradable characteristics. However, the yield of Zostera species available for ZA extraction is limited by natural factors, such as season, latitude, light, and temperature. Here we report the development of metabolically engineered Escherichia coli strains capable of producing ZA from glucose and glycerol. First, intracellular availability of the sulfur donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) was enhanced by knocking out the cysH gene responsible for PAPS consumption and overexpressing the genes required for PAPS biosynthesis. Co-overexpression of the genes encoding tyrosine ammonia-lyase, sulfotransferase 1A1, ATP sulfurylase, and adenosine 5'-phosphosulfate kinase constructed ZA producing strain with enhanced PAPS supply. Second, the feedback-resistant forms of aroG and tyrA genes (encoding 3-deoxy-d-arabinoheptulosonate 7-phosphate synthase and chorismate mutase, respectively) were overexpressed to relieve the feedback regulation of L-tyrosine biosynthesis. Third, the pykA gene involved in phosphoenolpyruvate-consuming reaction, the regulator gene tyrR, the competing pathway gene pheA, and the ptsHIcrr genes essential for the PEP:carbohydrate phosphotransferase system were deleted. Moreover, all genes involved in the shikimate pathway and the talA, tktA, and tktB genes in the pentose phosphate pathway were examined for ZA production. The PTS-independent glucose uptake system, the expression vector system, and the carbon source were also optimized. As a result, the best-performing strain successfully produced 1.52 g L-1 ZA and 1.30 g L-1p-hydroxycinnamic acid from glucose and glycerol in a 700 mL fed-batch bioreactor.

PC-Phos Enabled Catalytic Palladium-heteroallyl Asymmetric Cycloaddition.

Asymmetric cycloaddition reactions are the most powerful tool to the expeditious construction of enantioenriched cyclic motifs in organic chemistry. In sharp contrast to well-developed cycloaddition reactions via the palladium-trimethylenemethane (Pd-TMM) intermediate, hetero (3 + 2) cycloadditions of the heteroallyl cations remain rare, largely due to their thermally forbidden nature. To the best of our knowledge, there is no example of asymmetric version leading to enantioenriched heterocycles reported so far. Herein we enabled the first example of catalytic asymmetric (3 + 2) cycloaddition of electrophilic palladium-heteroallyl zwitterion intermediate (Pd-OTMM or Pd-NTMM) with cyclic or acyclic 1,3-dienes via a pathway terminated with C-N or C-O bond formation, delivering the highly substituted or fused pyrrolidine and tetrahydrofuran rings in high yields with excellent regio-, diastereo-, and enantioselectivity. Engineering the PC-Phos, one of the chiral sulfinamide phosphine (Sadphos) type ligands, by introducing the di-tert-butyl or/and 3,5-difluorophenyl group is a vital component in achieving excellent catalytic reactivity and enantioselectivity.

Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji-Trost of Benzotriazoles with 1,3-Dienes.

The asymmetric denitrogenative cycloaddition has emerged as a powerful tool to build chiral aza-heterocyles. However, only one example of asymmetric denitrogenative cycloaddition of benzotriazole with unsaturated hydrocarbons has been explored so far, because the ring-opening of benzotriazole to generate α-imino metal carbenoid species is a thermodynamically unfavorable process. We herein report an efficient asymmetric denitrogenative cycloaddition of benzotriazoles with cyclic and acyclic 1,3-dienes enabled by Pd and chiral sulfonamide phosphine ligand. A variety of substituted hexahydrocarbazoles and indolines were delivered in good yields with high ee values. Interestingly, a pair of enantiomers could be obtained with the use of Xu1 and PC2 with the same absolute configuration. The synthetic utilities of the optically active hexahydrocarbazoles were also showcased.

Simultaneous construction of axial and planar chirality by gold/TY-Phos-catalyzed asymmetric hydroarylation.

The simultaneous construction of two different chiralities via a simple operation poses considerable challenge. Herein a cationic gold-catalyzed asymmetric hydroarylation of ortho-alkynylaryl ferrocenes derivatives is developed, which enable the simultaneous construction of axial and planar chirality. The here identified TY-Phos derived gold complex is responsible for the high yield, good diastereoselectivity (>20:1 dr), high enantioselectivities (up to 99% ee) and mild conditions. The catalyst system also shows potential application in the synthesis of chiral biaryl compounds. The cause of high enantioselectivity of this hydroarylation is investigated with density functional theory caculation.

Depressive Symptoms among Junior High School Students in Southern China: Prevalence, Changes, and Psychosocial Correlates.

BACKGROUND: Depression is one of the most common mental health problems in adolescents. A careful assessment of the prevalence and risk of depressive symptoms, as well as those factors that protect against it, is essential for prevention and intervention programs. METHOD: Using two waves of data from Grade 7 to Grade 9 (N = 1,544 students in Wave 1), this study examined the prevalence and changes of depressive symptoms and their related psychosocial correlates (personal and familial factors, including family functioning and positive youth development [PYD] constructs) among junior high school students in Southern China. RESULTS: The results showed that while depressive symptoms generally declined throughout the secondary junior school years, symptoms of major depression remained stable. Concurrently, academic achievement, family functioning, and PYD constructs regarding cognitive behavioral competence (CBC), positive identity (PIT), and general PYD qualities (GPYDQ) negatively predicted depressive symptoms in Wave 1. Longitudinally, being female, having poor academic achievement and family functioning, and having a low PIT in Wave 1 significantly predicted depressive symptoms in Wave 2. LIMITATIONS: This study used the self-reporting approach, did not track a long-term developmental trajectories of adolescent depressive symptoms, and did not cover all potential predictors. CONCLUSIONS: The findings suggest that being female and having poor academic achievement are risk factors, while positive family functioning and PYD constructs protect against the development of adolescent depression.

The Prevalence and Socio-Demographic Correlates of Depressive Symptoms in Early Adolescents in China: Differences in Only Child and Non-Only Child Groups.

This study explores the prevalence and socio-demographic correlates of depressive symptoms in early adolescents in China, as well as the differences between an only child and non-only child group. A total of 2059 seventh-grade Chinese students were invited to complete a questionnaire, which included questions concerning socio-demographic factors, family function, and the Center for Epidemiological Studies Depression Scale (CES-D). The results revealed the following things. (1) thirty-four point seven percent of the participating Chinese early adolescents display symptoms of depression according to Radloff's criteria. Differences are significant across the four dimensions (i.e., positive affect, negative affect, somatic symptoms and retarded activity, and interpersonal difficulties), as well as across total scores between only children and children with sibling(s). (2) Academic achievement, having sibling(s) or not, migration, and family function can significantly predict depressive symptoms. (3) Two significant interactions were found, which were between sibling(s) and gender as well as sibling(s) and family function. Girls from the non-only child group and adolescents from the only child group with poor family function were more likely to have depressive symptoms. These findings suggest that a greater focus should be placed on girls from non-only child families, academic under-performers, migrants, and adolescents from poor family environments, and especially only children, to prevent or reduce the propensity for depressive symptoms.

Comparative Investigation into Formycin A and Pyrazofurin A Biosynthesis Reveals Branch Pathways for the Construction of C-Nucleoside Scaffolds.

Formycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside antibiotics in which ribose and a pyrazole-derived base are linked by a C-glycosidic bond. However, the logic underlying the biosynthesis of these molecules has remained largely unexplored. Here, we report the discovery of the pathways for FOR-A and PRF-A biosynthesis from diverse actinobacteria and propose that their biosynthesis is likely initiated by a lysine N6-monooxygenase. Moreover, we show that forT and prfT (involved in FOR-A and PRF-A biosynthesis, respectively) mutants are correspondingly capable of accumulating the unexpected pyrazole-related intermediates 4-amino-3,5-dicarboxypyrazole and 3,5-dicarboxy-4-oxo-4,5-dihydropyrazole. We also decipher the enzymatic mechanism of ForT/PrfT for C-glycosidic bond formation in FOR-A/PRF-A biosynthesis. To our knowledge, ForT/PrfT represents an example of ß-RFA-P (ß-ribofuranosyl-aminobenzene 5'-phosphate) synthase-like enzymes governing C-nucleoside scaffold construction in natural product biosynthesis. These data establish a foundation for combinatorial biosynthesis of related purine nucleoside antibiotics and also open the way for target-directed genome mining of PRF-A/FOR-A-related antibiotics.IMPORTANCE FOR-A and PRF-A are C-nucleoside antibiotics known for their unusual chemical structures and remarkable biological activities. Deciphering the enzymatic mechanism for the construction of a C-nucleoside scaffold during FOR-A/PRF-A biosynthesis will not only expand the biochemical repertoire for novel enzymatic reactions but also permit target-oriented genome mining of FOR-A/PRF-A-related C-nucleoside antibiotics. Moreover, the availability of FOR-A/PRF-A biosynthetic gene clusters will pave the way for the rational generation of designer FOR-A/PRF-A derivatives with enhanced/selective bioactivity via synthetic biology strategies.

Ligand and counteranion enabled regiodivergent C-H bond functionalization of naphthols with α-aryl-α-diazoesters.

Here, an unprecedented ligand and counteranion-controlled and site-selectivity switchable direct C-H bond functionalization of unprotected naphthols with α-aryl-α-diazoesters was developed. In this transformation, site selectivities are realized by turning on/off the coordination between metal complexes and hydroxy groups. The preliminary mechanism revealed that the interaction between the hydroxy group and gold catalyst plays a key role in switching the site-selectivity of gold-carbene. This protocol potentially provides a novel design for C-H bond functionalization.

Pd/PC-Phos-Catalyzed Enantioselective Intermolecular Denitrogenative Cyclization of Benzotriazoles with Allenes and N-Allenamides.

Reported herein is an asymmetric Pd/PC-Phos-catalyzed denitrogenative cyclization of benzotriazoles with allenes and N-allenamides, representing the first example of enantioselective denitrogenative cyclizations of benzotriazoles. A series of optically active 3-methyleneindolines were obtained in good yields with high ee values. The use of inexpensive and readily available starting materials, high regio- and enantioselectivity, a broad substrate scope, mild reaction conditions, no need for base, as well as versatile functionalization of the 3-methyleneindolines make this approach attractive.

Qualitative research investigating the mental health care service gap in Chinese burn injury patients.

BACKGROUND: Psychological disturbances are prevalent in people with burn injuries; however, psychological services are rarely accessiblepost-burn injury in China. The objective of this qualitative study was to explore and conceptualize the obstacles to delivering mental health care in burn injury patients. METHODS: The researchers used a grounded theory research approach to interview sixteen burn injury patients, five nurses, four rehabilitation therapists, five medical doctors, and eight caregivers regarding their experiences with current health care services and barriers. RESULTS: An explorative model was generated from the data, and the relationships among the categories were identified. People's beliefs, knowledge, socioeconomic status, cultural understanding of mental health, and social stigma appear to play key roles in the public health approach to post-burn health promotion and post-burn psychosocial interventions. CONCLUSION: The model proposed in our research highlights the need to focus on the underlying social, economic, and cultural determinants of mental health care. The underlying social determinants of the mental health care gap that is responsible for the ill-prepared health care must be addressed.

Gold(I)/Xiang-Phos-Catalyzed Asymmetric Intramolecular Cyclopropanation of Indenes and Trisubstituted Alkenes.

The first intramolecular enantioselective cyclopropanation of indenes and trisubstituted alkenes was accomplished by using new chiral phosphine X5 derived gold(I) complexes. This reaction is a straightforward, efficient method for constructing [5-3-6] fused-ring compounds with two vicinal all-carbon quaternary stereogenic centers, a core structure shared by numerous pharmacological products, and bioactive compounds. The salient features of this transformation include high enantioselectivity (up to >98% ee), excellent yield (>97%), and nice functional group tolerance.

Discovery and characterization of the tubercidin biosynthetic pathway from Streptomyces tubercidicus NBRC 13090.

BACKGROUND: Tubercidin (TBN), an adenosine analog with potent antimycobacteria and antitumor bioactivities, highlights an intriguing structure, in which a 7-deazapurine core is linked to the ribose moiety by an N-glycosidic bond. However, the molecular logic underlying the biosynthesis of this antibiotic has remained poorly understood. RESULTS: Here, we report the discovery and characterization of the TBN biosynthetic pathway from Streptomyces tubercidicus NBRC 13090 via reconstitution of its production in a heterologous host. We demonstrated that TubE specifically utilizes phosphoribosylpyrophosphate and 7-carboxy-7-deazaguanine for the precise construction of the deazapurine nucleoside scaffold. Moreover, we provided biochemical evidence that TubD functions as an NADPH-dependent reductase, catalyzing irreversible reductive deamination. Finally, we verified that TubG acts as a Nudix hydrolase, preferring Co2+ for the maintenance of maximal activity, and is responsible for the tailoring hydrolysis step leading to TBN. CONCLUSIONS: These findings lay a foundation for the rational generation of TBN analogs through synthetic biology strategy, and also open the way for the target-directed search of TBN-related antibiotics.

Effects of Mindfulness-Based Stress Reduction on Depression in Adolescents and Young Adults: A Systematic Review and Meta-Analysis.

Background: Mindfulness as a positive mental health intervention approach has been increasingly applied to address depression in young people. This systematic review and meta-analysis evaluated the effects of mindfulness-based stress reduction (MBSR) in the treatment of depression among adolescents and young adults. Methods: Electronic databases and references in articles were searched. Randomized controlled trials (RCTs) evaluating MBSR and reporting outcomes for depressive symptoms among young people aged 12 to 25 years were included. Data extraction and risk of bias assessment were conducted by two reviewers independently. Hedges' g with a 95% confidence interval was calculated to represent intervention effect. Results: Eighteen RCTs featuring 2,042 participants were included in the meta-analysis. Relative to the control groups (e.g., no treatment, treatment as usual, or active control), MBSR had moderate effects in reducing depressive symptoms at the end of intervention (Hedges' g = -0.45). No statistically significant effects were found in follow-up (Hedges' g = -0.24) due to a lack of statistical power. Meta-regression found that the average treatment effect might be moderated by control condition, treatment duration, and participants' baseline depression. Conclusion: MBSR had moderate effects in reducing depression in young people at posttest. Future research is needed to assess the follow-up effects of MBSR on depressive symptoms among adolescents and young adults.

Palladium/PC-Phos-Catalyzed Enantioselective Arylation of General Sulfenate Anions: Scope and Synthetic Applications.

Herein we reported an efficient palladium-catalyzed enantioselective arylation of both alkyl and aryl sulfenate anions to deliver various chiral sulfoxides in good yields (up to 98%) with excellent enantioselectivities (up to 99% ee) by the use of our developed chiral O,P-ligands (PC-Phos). PC-Phos are easily prepared in short steps from inexpensive commercially available starting materials. The single-crystal structure of the PC4/PdCl2 showed that a rarely observed 11-membered ring was formed via the O,P-coordination with the palladium(II) center. The salient features of this method include general substrate scope, ease of scale-up, applicable to the late-stage modification of bioactive compounds, and the synthesis of a marketed medicine Sulindac.

Gold-Catalyzed Asymmetric Intramolecular Cyclization of N-Allenamides for the Synthesis of Chiral Tetrahydrocarbolines.

Highly enantioselective gold-catalyzed intramolecular cyclization of N-allenamides was implemented by utilizing a designed chiral sulfinamide phosphine ligand (PC-Phos). This represents the first example of highly enantioselective intramolecular cyclization of N-allenamides. The practicality of this reaction was validated in the total synthesis of (R)-desbromoarborescidine A and formal synthesis of (R)-desbromoarborescidine C and (R)-deplancheine. Moreover, the catalyst system PC-Phos/AuNTf2 proved to be specifically efficient to promote the desymmetrization of N-allenamides in excellent yields with satisfactory ee values.

The Trauma of Birth or Parenting a Child: Effect on Parents' Negative Emotion in China.

The present study assessed negative emotions associated with the traumas of infertility and child rearing (child's disability or death) and the correlates of duration of trauma. The widely used Chinese Mental Health Scale was used to assess negative emotions in 294 individuals who experienced the aforementioned traumas and 124 who did not (control group). Results showed that individuals with infertility exhibited greater anxiety, depression, and solitude than the control group; bereaved parents and had greater solitude and fear than control group; and parents of children with disabilities had greater solitude than the control group. Parents who experienced the death of a child had more fear and physiological maladjustment than parents of a child with disabilities. In addition, individuals without parenting experience had higher scores on solitude, fear, and physiological disease than those with parenting experience. After controlling for demographic variables, the duration of trauma significantly negatively predicted depression in the infertile group and for bereaved parents. The results suggest that in order to prevent psychological and physiological health problems among infertile couples, parents of a disabled child, and parents who experience the death of child, family and community-based strategies should be developed and implemented.

Screening for Postpartum Depression and Associated Factors Among Women in China: A Cross-Sectional Study.

Objectives: This study examined what percentage of Chinese mothers during a three-year postpartum period were screened for postpartum depression and explored the correlation between postpartum depression and various socio-demographic, psychological, and cultural factors. Study design: Cross-sectional survey. Methods: A total of 506 mothers 23 years of age and older who were within three years postpartum completed the online survey. The survey collected information such as family economic status, a history of depression, preparation for pregnancy, relationships with husbands, and family members, adult attachment types (Adult Attachment Scale, AAS), and depression (The Center for Epidemiologic Studies Depression Scale, CESD). Results: Approximately 30% of mothers 1-3 years postpartum reported symptoms above the CESD cut-off score (≥16 scores) associated with the risk for depression (28.0% in the first year, 30.8% in the second year, and 31.8% in the third year). Factors significantly associated with depression in participants in the correlation analysis were education level; family income; preparation for pregnancy; a history of depression; amount of time spent with their husbands; relationships with husbands, parents, and parents-in-law; and a close, dependent, and/or anxious attachment style. Multiple regression analyses revealed that a history of depression; less preparation for pregnancy; poorer relationships with husbands, parents, and parents-in-law; and a more anxious attachment style were strongly related to a higher risk of postpartum depression. Conclusion: The overall percentage of mothers after delivery who were vulnerable to depression in China remains high. Various factors were significant predictors of postpartum depression. The research findings have several valuable implications for intervention practices. For example, attachment styles and depression history in the assessments of perinatal depression could improve screenings and the design of interventions. Additionally, improving the family relationships and family environments of women post-delivery may be promising approach for postpartum depression prevention or intervention.

Internet Addiction Among College Students in China: Prevalence and Psychosocial Correlates.

This study examined the prevalence of Internet addiction among college students in China and explored the correlations between Internet addiction and psychosocial factors. A total of 1,173 Chinese college students (62.1 percent males, Mage = 19.65 years) were invited to complete a questionnaire containing measures of demographic characteristics, psychosocial correlates, including the quality of the parent-child relationship, propensity for depression, and psychosocial competence, and Internet addictive behaviors. Among the participating students, 15.2 percent were classified as having Internet addiction. Furthermore, students who reported poorer parent-child relationships, higher levels of depression, and lower levels of psychosocial competence were more likely to report behaviors indicative of Internet addiction. Internet addiction was prevalent among college students in China. The significant predictors of Internet addiction were found to include the quality of the family environment (i.e., the quality of the parent-child relationship), personal mental health status (i.e., the existence of depression), and the level of developmental assets (i.e., psychosocial competence). These findings suggest that improving the quality of family life and promoting psychosocial competence among youth can be promising approaches for preventing or/and reducing Internet addiction among college students in China.

Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and Allenes: Stereospecific Synthesis of Chiral Pyrrolidines.

The first rhodium-catalyzed intermolecular [3+2] cycloaddition reaction of vinyl aziridines and allenes for the synthesis of enantioenriched functionalized pyrrolidines was realized. [3+2] cycloaddition with the proximal C=C bond of N-allenamides gave 3-methylene-pyrrolidines in high regio- and diastereoselectivity, whereas, 2-methylene-pyrrolidines were obtained as the major products by the cycloadditions of vinyl aziridines with the distal C=C bond of allenes. Use of readily available starting materials, a broad substrate scope, high selectivity, mild reaction conditions, as well as versatile functionalization of the cycloadducts make this approach very practical and attractive.