Bisubstrate inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: Transition state analogs for high affinity binding.

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate biosynthesis pathway. It catalyzes pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP). HPPK is essential for microorganisms but absent in mammals; therefore, it is an attractive target for developing novel antimicrobial agents. Previously, based on our studies of the structure and mechanism of HPPK, we created first-generation bisubstrate inhibitors by linking 6-hydroxymethylpterin to adenosine through phosphate groups, and developed second-generation inhibitors by replacing the phosphate bridge with a linkage that contains a piperidine moiety. Here, we report third-generation inhibitors designed based on the piperidine-containing inhibitor, mimicking the transition state. We synthesized two such inhibitors, characterized their protein-binding and enzyme inhibition properties, and determined their crystal structures in complex with HPPK, advancing the development of such bisubstrate analog inhibitors.

[Long-term effect and safety of non-occlusive intra-vas device for male contraception].

OBJECTIVE: To assess the long-term effect and safety of non-occlusive intra-vas device (IVD) for male contraception in comparison with no-scalpel vasectomy (NSV). METHODS: We conducted a follow-up investigation on 100 males who had received IVD and another 50 who had undergone NSV 6 years before. We compared the rates of sperm absence and complications between the two groups. RESULTS: Follow-up visits were successfully performed on 95 males (95%) of the IVD group and 44 (88%) of the NSV group. Pregnancy was not found in any of the cases. Spermatozoa (> or = 5 x 10(6)/ml) were not detected in 87 cases (91.58%) in the IVD group and in 44 cases (95.45%) in the NSV group, with no significant differences between the two groups (P > 0.05). The rate of postoperative complications in the IVD group (11.58%) showed no significant difference from that of the NSV group (4.55%) (P > 0.05). CONCLUSION: IVD is as effective and safe as NSV for male contraception.

Emerging Hypervirulent Marek's Disease Virus Variants Significantly Overcome Protection Conferred by Commercial Vaccines.

As one of the most important avian immunosuppressive and neoplastic diseases, Marek's disease (MD), caused by oncogenic Marek's disease virus (MDV), has caused huge economic losses worldwide over the past five decades. In recent years, MD outbreaks have occurred frequently in MD-vaccinated chicken flocks, but the key pathogenic determinants and influencing factors remain unclear. Herein, we analyzed the pathogenicity of seven newly isolated MDV strains from tumor-bearing chickens in China and found that all of them were pathogenic to chicken hosts, among which four MDV isolates, SDCW01, HNXZ05, HNSQ05 and HNSQ01, were considered to be hypervirulent MDV (HV-MDV) strains. At 73 days of the virus infection experiment, the cumulative incidences of MD were 100%, 93.3%, 90% and 100%, with mortalities of 83.3%, 73.3%, 60% and 86.7%, respectively, for the four viruses. The gross occurrences of tumors were 50%, 33.3%, 30% and 63.3%, respectively, accompanied by significant hepatosplenomegaly and serious atrophy of the immune organs. Furthermore, the immune protection effects of four commercial MD vaccines against SDCW01, CVI988, HVT, CVI988+HVT, and 814 were explored. Unexpectedly, during the 67 days of post-virus challenge, the protection indices (PIs) of these four MD vaccines were only 46.2%, 38.5%, 50%, and 28%, respectively, and the birds that received the monovalent CVI988 or HVT still developed tumors with cumulative incidences of 7.7% and 11.5%, respectively. To our knowledge, this is the first demonstration of the simultaneous comparison of the immune protection efficacy of multiple commercial MD vaccines with different vaccine strains. Our study revealed that the HV-MDV variants circulating in China could significantly break through the immune protection of the classical MD vaccines currently widely used. For future work, there is an urgent need to develop novel, more effective MD vaccines for tackling the new challenge of emerging HV-MDV strains or variants for the sustainable control of MD.

Families, Schools, and the Longitudinal Changes in Psychological Distress among College Students during the First Year of the COVID-19 Pandemic: Evidence from a National Panel Survey in China.

BACKGROUND: The psychological well-being of students in higher education has become an increasingly important concern in the context of the COVID-19 pandemic. The majority of prior studies were cross-sectional and thereby failed to capture the individual changes in mental health over time. Moreover, few studies have explored whether and how socioeconomic and education backgrounds could be related to college students' mental health changes. This study aimed to fill these gaps. METHODS: Data were from a nationwide, two-wave panel survey of college students in China. Baseline information was collected in November 2019, i.e., before the outbreak of the COVID-19 epidemic in China. A follow-up survey was conducted in November and December 2020, when the epidemic was effectively contained in mainland China. In both waves, mental health was assessed with the 10-item Kessler Psychological Distress Scale (K10). The between-wave changes in psychological distress were measured and categorized. RESULTS: Overall, 13.5% of students experienced at least a one-standard-deviation increase in psychological distress over the one-year follow-up. Results from both bivariate and multivariable analysis showed that this marked distress increase was more pronounced among vocational college students (vs. academic undergraduate and postgraduate students) and those with lower levels of academic performance. In contrast, family socioeconomic status (as measured by parental education, family economic condition, and current residence) was not associated with distress changes over time. CONCLUSIONS: These findings highlight the importance of the educational disparities within the higher education system in understanding the mental health dynamics of college students in the context of the COVID-19 pandemic.

Water-medium and solvent-free organic reactions over a bifunctional catalyst with Au nanoparticles covalently bonded to HS/SO3H functionalized periodic mesoporous organosilica.

An operationally simple approach for the preparation of a new class of bifunctional Au nanoparticle-acid catalysts has been developed. In situ reduction of Au(3+) with HS-functionalized periodic mesoporous organosilicas (PMOs) creates robust, fine Au nanoparticles and concomitantly produces a sulfonic acid moiety strongly bonded to PMOs. Characterizations of the nanostructures reveal that Au nanoparticles are formed with uniformed, narrow size distribution around 1-2 nm, which is very critical for essential catalytic activities. Moreover, the Au nanoparticles are mainly attached onto the pore surface rather than onto the outer surface with ordered mesoporous channels, allowing for maximal exposure to reaction substrates while minimizing Au nanoparticle leaching. Their higher S(BET), V(P), and D(P) than either the Au-HS-PMO(Et) or the Au/SO(3)H-PMO(Et) render the catalyst with comparably even higher catalytic efficiency than its homogeneous counterparts. Furthermore, the unique amphiphilic compartment of the Au-HS/SO(3)H-PMO(Et) nanostructures enables organic reactions to proceed efficiently in a pure aqueous solution without using any organic solvents or even without water. As demonstrated experimentally, remarkably, the unique bifunctional Au-HS/SO(3)H-PMO(Et) catalyst displays higher efficiencies in promoting water-medium alkyne hydration, intramolecular hydroamination, styrene oxidation, and three-component coupling reactions and even the solvent-free alkyne hydration process than its homogeneous catalysts. The robust catalyst can be easily recycled and used repetitively at least 10 times without loss of catalytic efficiency. These features render the catalyst particularly attractive in the practice of organic synthesis in an environmentally friendly manner.

Periodic mesoporous organometallic silicas with unary or binary organometals inside the channel walls as active and reusable catalysts in aqueous organic reactions.

A new type of heterogenized organometallic catalysts, periodic mesoporous organometallic silicas with organometals and organic groups embedded in silica walls have been developed using surfactant-directed co-condensation. These catalysts exhibit high efficiencies and strong durability in water-medium organic reactions. Moreover, a bifunctional catalyst containing both Pd(II) and Ru(II) organometals inside pore walls can catalyze the water-medium "one-pot" cascade reaction effectively. These catalysts can be conveniently recycled and reused without significant loss of catalytic activities.

[Analysis of disease types of outpatients with intestinal diseases from two grade-three general hospitals in Beijing].

OBJECTIVE: To understand the spectrum of diseases and epidemiological characteristics of outpatients at Entric Disease Clinic, with a focus on analysis of the distribution of infectious diarrheal diseases in different populations and to explore disease control strategies on Enteric Infectious Diseases for focal groups. METHODS: A census on outpatients at Entric Disease Clinics was conducted in two class Three comprehensive hospitals in Beijing from April 1 to October 31, 2009 based on a descriptive study using diarrhea-syndrome surveillance system set in the two clinics, thus to depict the spectrum of diseases and epidemiological characteristics of outpatients, and analyze the proportion of infectious diarrhea in diarrheal diseases specifically and the rate changes of infectious diarrhea in different months, age groups and occupational groups. RESULTS: Diseases are varied at the two enteric diseases clinics among the patients and there are mainly 10 kinds of diseases, "non-infectious diarrhea" accounted for the highest percentage (77.4%), followed by "unspecified diarrhea" (11.7%), and infectious diarrhea accounted for the least proportion(8.7%)."Gastroenteritis and enteritis" are the most frequently diagnosed cases among all the diseases, was a total of 7 565 cases, accounting for 70.2%. The volume of visits reached its top during summer and autumn(July to September), and the mean volume of visits in this period is (60.78+/-16.85) cases/day. The volume of visits has an obvious seasonal trend, and visits during July and August are the most frequent (41.82% altogether). Patients with "infectious diarrhea" had a highest ratio(5.3%) in May and lowest (1.1%) in October while patients with "bacillary dysentery" accounted for a highest ratio(8.2%) in September and lowest(3.8%) in April. Outpatients are mainly from Beijing city(61.9%), in which young and middle-aged people accounted for 73.9% in total, and student is the main occupation (28.8%). The distributions of diarrheal diseases are the same in different age groups but differ from different occupational groups. Infectious diarrhea accounted for a highest proportion(9.2%) in 18-to-44-year-old age group when using age grouping, and a highest proportion(15.2%) in restaurant service personnel when using occupation grouping. CONCLUSION: The volume of outpatients attended at general hospitals is overwhelming especially in July and August, and the major type is "non-infectious diseases", which indicates an arduous task on prevention and control of Enteric Infectious Diseases. Infectious diarrhea took up a certain amount, but the rate is not that high, which indicates possible missing diagnosis of patients with infectious diseases.Our focal groups would be young and middle-aged people and students in the city. Therefore, the need to extend the consultation hours is urgent. Meanwhile, for the main goal of surveillance and early warning on Enteric Infectious Diseases, all aspects of construction of Enteric Disease Clinic should be strengthened, such as enhance laboratory tests on pathogens, improve diagnosis level of physicians and etc.

An ultrasonic-assisted synthesis of rice-straw-based porous carbon with high performance symmetric supercapacitors.

Biomass porous carbon materials are ideal supercapacitor electrode materials due to their low price, rich source of raw materials and environmental friendliness. In this study, an ultrasonic-assisted method was applied to synthesize the rice-straw-based porous carbon (UPC). The obtained UPC exhibited a two-dimensional structure and high specific surface area. In addition, the electrochemical test results showed that the UPC with a 1 hour ultrasonic treatment and lower activation temperature of 600 °C (UPC-600) demonstrated optimal performance: high specific capacitances of 420 F g-1 at 1.0 A g-1 and 314 F g-1 at a high current of 10 A g-1. Significantly, the symmetric supercapacitors showed a high energy density of 11.1 W h kg-1 and power density of 500 W kg-1. After 10 000 cycles, 99.8% of the specific capacitance was retained at 20 A g-1. These results indicate that UPC-600 is a promising candidate for supercapacitor electrode materials.

Nef mutations in long-term non-progressors from former plasma donors infected with HIV-1 subtype B in China.

OBJECTIVE: To study the specific amino acid variation in Nef that may be related to disease progression after infection with HIV-1 subtype B, a predominant strain circulating in China, and to determine whether changes in Nef secondary structure may influence different stages of AIDS development based on the concept that the Nef gene of HIV infection dramatically alter the severity of viral infection and virus replication and disease progression, and that long-term non-progressors (LTNP) of HIV infection are commonly associated with either a deletion of the Nef gene or the defective Nef alleles. METHODS: The study subjects were divided into LTNP1(n=14), LTNP2 (n=16) and slow progressor (SP, n=19) groups for mutational analysis of the Nef sequence. The data were obtained by using Bioedit, MEGA, Anthewin and SAS software. RESULTS: Residues in Nef TA(48/49) and K151 occurred more frequently in the LTNP group while AA(48/49) was more frequently observed in the SP group. Of the differences observed in the secondary structure comparison using Nef consensus sequences of these three groups, one was roughly corresponding to the Nef(48/49) mutation site. CONCLUSION: TA(48/49), K(151), and AA(48/49) in the Nef gene might be associated with the different stages of HIV infection, and there may be a link between the Nef secondary structure and the progression of HIV-1 infection.

3-Phenyl-2-thioxo-1,3-thia-zolidin-4-one.

In the mol-ecule of the title compound, C(9)H(7)NOS(2), the heterocycle and the phenyl ring are oriented at a dihedral angle of 72.3 (1)°. Adjacent mol-ecules are connected through C-H⋯O inter-actions.

Ethyl 3,7-dichloro-quinoline-8-carboxyl-ate.

The title compound, C(12)H(9)Cl(2)NO(2), was prepared by the esterification of 3,7-dichloro-quinoline-8-carboxylic acid with triethyl phosphite. The crystal structure is stabilized by aromatic π-π stacking between the benzene and the pyridine rings of neighbouring mol-ecules [centroid-centroid distances = 3.716 (2) and 3.642 (2) Å]. In addition, weak inter-molecular C-H⋯N hydrogen bonds are present in the structure.

High Prevalence of Macrolide-resistance and Molecular Characterization of Streptococcus pyogenes Isolates Circulating in China from 2009 to 2016.

Streptococcus pyogenes, or group A Streptococcus, is a pathogen responsible for a wide range of clinical manifestations, from mild skin and soft tissue infections and pharyngitis to severe diseases. Its epidemiological characteristics should be comprehensively under surveillance for regulating the national prevention and treatment practice. Herein, a total of 140 S. pyogenes, including 38 invasive and 102 noninvasive isolates, were collected from infected patients in 10 tertiary general hospitals from 7 cities/provinces in China during the years 2009-2016. All strains were characterized by classical and molecular techniques for its emm types/subtypes, virulent factors and antibiotic resistance profiling. Of 140 isolates, 15 distinct emm types and 31 subtypes were detected, dominated by emm12 (60 isolates, 42.9%), emm1(43, 30.7%), and emm89 (10, 7.1%), and 8 new emm variant subtypes were identified. All strains, invasive or not, harbored the superantigenic genes, speB and slo. The other virulence genes, smeZ, speF, and speC accounted for 96.4, 91.4, and 87.1% of collected isolates, respectively. Further multilocus sequence typing (MLST) placed all strains into 22 individual sequence types (STs), including 4 newly-identified STs (11, 7.9%). All isolates were phenotypically susceptible to penicillin, ampicillin, cefotaxime, and vancomycin, whereas 131(93.5%), 132(94.2%), and 121(86.4%) were resistant to erythromycin, clindamycin, and tetracycline, respectively. Our study highlights high genotypic diversity and high prevalence of macrolide resistance of S. pyogenes among clinical isolates circulating in China.

First molecular evidence of intrauterine and surgical-site infections caused by Streptococcus dysgalactiae subsp. equisimilis.

S. dysgalactiae subsp. equisimilis (SDSE) is infrequently associated with maternal infections during delivery in pregnant women. A rare case is presented of a woman with intrauterine infection and surgical-site infection due to SDSE after cesarean section, which had colonized her genital tract and, via the ascending pathway, reached her intact fetal membrane. All isolates were identified as Streptococcus Lancefield group G, and their emm genes that coded M protein belonged to stG6.1. The isolates tested negative for a series of streptococcal superantigen virulence genes but positive for nonsuperantigenic virulence genes. In particular, molecular typing using pulsed-field gel electrophoresis analysis disclosed that the three isolates from the different infection sites had identical profiles. Furthermore, multilocus sequence typing indicated that the three isolates belonged to a new sequence typing. Our results indicated that SDSE is potentially pathogenic for pregnant women and newborns if colonized.

Molecular characterization and antibiotic resistance of clinical Streptococcus dysgalactiae subsp. equisimilis in Beijing, China.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is presently considered as a human pathogen associated with clinical infection. We characterized 56 SDSE isolates collected from two tertiary hospitals in Beijing, China. Sixteen distinct emm types/subtypes were detected, dominated by stG245.0 (32.1%), stG652.0 (10.7%), stG6.1 (10.7%) and stG485.0 (10.7%), and a novel stG840.0 variant type was identified. All isolates possessed virulence genes of sagA and scpA, and most carried slo (98.2%), ska (98.2%) and speG(dys) (35.7%). By multilocus sequence typing (MLST) analysis, 17 individual sequence types (STs) were distinguished, including 7 newly-identified STs (26.8% of isolates), of which ST127 (30.4%), ST7 (12.5%) and ST44 (10.7%) dominated. Meanwhile, pulsed-field gel electrophoresis (PFGE) analysis revealed 33 pattern types (PTs), which were further combined into 16 pattern clusters (PCs), and 59.3% of isolates were distributed into 2 dominant PCs. Notably, emm types had both close relationship and consistency with STs and PFGE PCs. Furthermore, of 56 SDSE isolates, the predominant antibiotic resistances were erythromycin (71.4%), clindamycin (71.4%) and tetracycline (60.7%). Correspondingly, the prevalent resistance genes of macrolide and tetracycline were erm(B) (78.6%) and tet(M) (73.2%). In addition, multiple point mutations of parC, one of fluoroquinolone resistance genes, were observed (accounting for 75%), and were divided into 12 types, with parC 07 as the predominant type. Our data suggested the wide molecular diversity and distinctive regional features of SDSE from clinical infection in Beijing, China.

Molecular characteristics and antimicrobial resistance in invasive and noninvasive Group B Streptococcus between 2008 and 2015 in China.

Group B streptococcus (GBS) is an increasing pathogen threat to newborns and adults with immunodepressive diseases. Here, a total of 193 GBS, including 51 invasive and 142 noninvasive isolates, were collected from the patients with infections in 7 tertiary hospitals from 5 cities in China during the year 2008 to 2015. The strains of GBS were characterized by classical and molecular techniques for capsular polysaccharide serotyping, genes for pilus island (PI) and α-like protein (alp), and antibiotic resistance profiling. Of 193 isolates, the predominant serotypes were III (45.6%) and Ia (18.7%). All strains carried at least 1 PI gene. The combination of PI-2b and PI-1 was present in 46.1% isolates, followed by PI-2a alone (80, 41.5%) and PI-2b alone (23, 11.9%). The most prevalent alp gene was rib (87, 45.1%), followed by α-C (47, 24.4%), ε (33, 17.1%), alp2/3 (7, 3.6%) and alp4 (2, 1.0%), respectively. The clonal relationships between strains were investigated using multilocus sequence typing. The strains were distinguished into 26 individual sequence typing, and further clustered into 6 clonal complexes. A significant association was noted between the distributions of alp genes, serotyping and PI profiles, such as serotype III-rib-PI+PI-2a, Ib-α-C, and Ia-ε-PI-2a. No penicillin-resistant strains were detected, and 74.1%, 64.2%, and 68.9% were resistant to erythromycin, clindamycin, and tetracycline, respectively. The infective GBS isolates in China demonstrated epidemical features.

Crystal structures, spectra properties and DFT calculations studies on 4-phenyl-1-(3-phenylallylidene)thiosemicarbazide and its Ni(II) complex.

4-Phenyl-1-(3-phenylallylidene)thiosemicarbazide (HL) and its metal complex of NiL2 have been synthesized. For them, elemental analysis, IR and X-ray single crystal diffraction have been carried out. In complex NiL2, the central Ni(2+) ion coordinates with two deprotonated ligands of L(-) and adopts a distorted square planar configuration with the Ni(2+) ion being located at the inversion center. The thermal analyses result shows that complex NiL2 undergoes two decomposition processes. For the title compounds, DFT calculations of the structures and natural population analysis (NPA) have been performed at B3LYP/LANL2DZ level of theory. The predicted geometric parameters are compared with the experimental values and they are supported each other. By using TD-DFT method, electron spectra of ligand HL and complex NiL2 have been predicted, which suggest the B3LYP/LANL2DZ method can approximately simulate the electron spectra for the system presented here. The NPA results indicate that, for ligand HL, the electronic absorption spectra are mainly assigned to n-π(∗) and π-π(∗) electron transitions, while for the complex NiL2, the electronic transitions are mainly derived from the contribution of an intra-ligand (IL) transition, a metal-to-ligand charge transfer (MLCT) transition and a d-d transition. Based on vibrational analysis, thermodynamic properties for ligand HL and complex NiL2 at different temperatures have been obtained.

The first case of bacteraemia due to non-O1/non-O139 Vibrio cholerae in a type 2 diabetes mellitus patient in mainland China.

Bacteraemia due to non-O1/non-O139 Vibrio cholerae is rarely documented in mainland China. We report such a case in a 70-year-old male with type 2 diabetes mellitus. The clinical features, phenotypic analyses, and presence of a panel of known virulence genes in the isolated strain are described. To the best of our knowledge, this is the first reported case of bacteraemia due to this strain in a T2DM patient without other coexisting underlying diseases in mainland China.

Pleuritis due to Brevundimonas diminuta in a previously healthy man.

Brevundimonas diminuta is rarely associated with invasive infections. We report the case of a previously healthy young man with pleural effusion, in which B. diminuta was recovered but incorrectly identified as Kingella kingae when it was freshly isolated. Consequently, the misidentification resulted in initial treatment failure. The correct identification was achieved through further incubation, sequencing of the 16S rRNA gene and MS.

Study on the oxidation form of adenine in phosphate buffer solution.

The oxidation of adenine in phosphate buffer solution is investigated using square-wave voltammetry and in situ UV spectroelectrochemistry. The geometry of adenine and the derivatives optimized at DFTB3LYP-6-31G (d, p)-PCM level is in agreement with the crystal structure, and the imitated UV spectra of adenine and the product at electrode are consistent with the in situ UV spectra. The relationship between the electrochemical property and the molecular structure is also discussed. The experimental and theoretical results show that the adenine oxidation origins from the neutral adenine.