Objective To observe the clinical efficacy of the Mingmen eight array massage combined with compound lysine hydrochloride and zinc gluconate granules for the treatment of infantile diarrhea. Methods Totally 120 children with diarrhea met the inclusion criteria were divided into the treatment group, Western medicine group, and general massage group by random number table method, 40 cases in each group. All 3 groups were given dietary guidance and did moderate exercise. Western medicine group was administered orally for compound lysine hydrochloride and zinc gluconate granules, two bags per day for the aged 1–10, three bags per day for the aged >10. Treatment group was given the Mingmen eight array massage therapy based on Western medicine. General massage group received conventional massage therapy based on Western medicine, with four weeks as treatment course. 3 groups of patients were observed before and after treatment for salivary amylase, blood zinc value, urine D-xylose absorption and excretion test, TCM symptom score, and clinical efficacy were evaluated. Results There was statistical significance in the salivary amylase, blood zinc value, and urinary D-xylose absorption and excretion rate between before and after t reatment(P<0.05); after treatment, treatment group showed higher salivary amylase, blood zinc value, and urinary D- xylose absorption and excretion rate than the Western medicine group and general massage group (P<0.05); scores of diarrhea, loose stool, lassitude, lusterless complexion, and appetite reduction decreased compared with before treatment (P<0.05); after treatment, all integrals of treatment group were lower than Western medicine group and general massage group (P<0.05). The total effective rates of the treatment group, Western medicine group and general massage group were 92.50％ (37/40), 72.50％ (29/40), and 75％ (30/40) respectively. There was statistical significance among the three groups (P<0.05). Conclusion Mingmen eight array massage combined with compound lysine hydrochloride and zinc gluconic granules can effectively alleviate the clinical symptoms of patients with infantile diarrhea, and improve the level of laboratory parameters.

Objective:To translate the Attention to Positive and Negative Inventory(APNI)and analyze the validity and reliability in Chinese undergraduates sample,to offer a convenient and reliable tool of measuring the cognitive bias for national researchers. Methods:The English-version APNI went through translation into Chinese, retroversion into English,translation into Chinese again,and revision several stages. Two parts of samples (1450 Chinese college students)were surveyed. Sample one (n=1000)was used for item analysis,exploratory factor a-nalysis (EFA),concurrent validity and reliability analysis,while sample 2 (n=450)was used for confirmatory fac-tor analysis (CFA). Totally 68 subjects of sample 1 were randomly chosen and resurveyed with an interval of one week. Beck depression inventory (BDI-II)and patient health questionnaire (PHQ-9)was used for concurrent validi-ty. Results:Item analysis indicated that the 22 items of Chinese APNI had good discriminability. EFA focused onattention to positive information(API)and attention to negative information(ANI)two factors. CFA showed good model fit (χ2 =1376,RMESA=0. 09,CFI=0. 94). Concurrent validity result showed that the total scores of BDI-II and PHQ-9 was negatively correlated with total scores of API (r=-0. 24,-0. 29,Ps<0. 01 ),and posi-tively correlated with total scores of ANI (r=0. 36,0. 31,Ps<0. 01). The Cronbach'αcoefficients of API and ANI sub-scale were 0. 86 and 0. 82,while the retest reliability coefficients were 0. 79 and 0. 62. Conclusion:It suggests that the Chinese APNI has good validity and reliability in a sample of college students,which could be used to eval-uate the cognitive bias of Chinese college students.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

Antiviral Agents/pharmacology* ; COVID-19 ; Coronavirus 3C Proteases ; Humans ; Lactams ; Leucine ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Nitriles ; Proline ; Protease Inhibitors/pharmacology* ; SARS-CoV-2

Heme/metabolism* ; Cryoelectron Microscopy ; Membrane Transport Proteins ; Escherichia coli Proteins/metabolism*

Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins