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The distribution of the incubation period of the novel coronavirus disease that emerged in 2019 (COVID-19) has crucial clinical implications for understanding this disease and devising effective disease-control measures. Qin et al. (2020) designed a cross-sectional and forward follow-up study to collect the duration times between a specific observation time and the onset of COVID-19 symptoms for a number of individuals. They further proposed a mixture forward-incubation-time epidemic model, which is a mixture of an incubation-period distribution and a forward time distribution, to model the collected duration times and to estimate the incubation-period distribution of COVID-19. In this paper, we provide sufficient conditions for the identifiability of the unknown parameters in the mixture forward-incubation-time epidemic model when the incubation period follows a two-parameter distribution. Under the same setup, we propose a likelihood ratio test (LRT) for testing the null hypothesis that the mixture forward-incubation-time epidemic model is a homogeneous exponential distribution. The testing problem is non-regular because a nuisance parameter is present only under the alternative. We establish the limiting distribution of the LRT and identify an explicit representation for it. The limiting distribution of the LRT under a sequence of local alternatives is also obtained. Our simulation results indicate that the LRT has desirable type I errors and powers, and we analyze a COVID-19 outbreak dataset from China to illustrate the usefulness of the LRT., 34 pages, 2 figures, 2 tables

Background: The COVID-19 outbreak is a serious concern and has caused a great loss to the global economy. Therefore, COVID-19 has become an urgent public health problem. Although new vaccines and small molecule drugs are now available, these prevention and treatment methods cannot completely control the epidemic due to the constant mutation of SARS-CoV-2. Targeting 3CLpro/RdRp is expected to develop drugs that are not susceptible to the mutation of SARS-COV-2, and it will also have a certain effect on the coronavirus that may appear in the future. Objective: This study aimed to find small molecules against SARS-CoV-2 with research potential and provide relevant data for the rational development of anti-SARS-COV-2 drugs. Methods: Targeting 3CLpro/RdRp, using Shards database (120,000 natural small molecule compounds) in the ZINC database, adopting a step-by-step screening strategy, and taking Lopinavir, Indinavir, and Molnupiravir as screening criteria was done. Moreover, the top scoring compounds were screened using rigid docking, and molecular dynamics simulation and ADME prediction were performed. Finally, the molecules with better scores were screened out. Results: After molecular docking with 3CLpro as the target, 3207 compounds meeting the screening criteria were obtained. After applying Lipinski's rule of five for drug property screening, 1825 compounds that met the criteria were obtained. After molecular docking with RdRp as the target, ZINC04259665 has a good docking score. According to molecular dynamics simulation results, ZINC04259665 is stable in combination with 3CLpro/RdRp. ADME prediction shows that ZINC04259665 has good druggability. Conclusion: Using 3CLpro/RdRp targets and then using a step-by-step strategy to screen the compound with the highest score through molecular dynamics simulation and ADME prediction, it was found that ZINC04259665 has good development potential and can be used as a follow-up hit compound for research. In addition, the data obtained provide relevant information for the rational development of anti- SARS-COV-2 drugs.

Objectives: Major depressive disorder (MDD) has been reported to affect an increasing number of individuals due to the modern lifestyle. Because of its complicated mechanisms and recurrent attacks, MDD is considered a refractory chronic disease. Although the mainstream therapy for MDD is chemical drugs, they are not a panacea for MDD because of their expensiveness, associated serious adverse reactions, and endless treatment courses. Hence, we studied three kinds of herbal medicines, namely, Panax ginseng C.A. Mey (PGM), Bupleurum chinense DC (BCD), and Gastrodia elata Blume (GEB), and reviewed the mechanisms underlying their antidepressant properties to provide a reference for the development of antidepressants and clinical medications. Methods: An extensive range of medicinal, clinical, and chemistry databases and search engines were used for our literature search. We searched the literature using certain web literature search engines, including Google Scholar, PubMed, Science Direct, CNKI (China National Knowledge Infrastructure), and Web of Science Results: Experimental research found that active compounds of these three medicines exhibited good antidepressant effects in vivo and in vitro. Clinical investigations revealed that single or combined treatment of these medicines improved certain depressive symptoms. Antidepressant mechanisms are summarized based on this research. Conclusion: The antidepressant mechanism of these three medicines includes but is not limited to ameliorating inflammation within the brain, reversing the hypothalamic-pituitary adrenal axis (HPA) system hyperfunction, inhibiting monoamine neurotransmitters reuptake, anti-neuron apoptosis and preventing neurotoxicity, and regulating depressive-related pathways such as the BDNF pathway and the PI3K/Akt/mTOR pathway.

Two efficient, scalable routes to bis-1,2,4-oxadiazole have been developed by tandem Staudinger/aza-Wittig reaction from the same starting material diaziglyoxime, isocyanates and triphenylphosphonium in good yields. Background: Two convenient and efficient routes for the synthesis of diamino derivatives of bis-1,2,4-oxadiazoles were described. Objective: This study provides a simple protocol for the synthesis of bis-1,2,4-oxadiazoles. Methods: The two procedures were based on tandem Staudinger/aza-Wittig reaction from the same starting material diaziglyoxime, isocyanates and triphenylphosphorus. Results: In synthesis method I, diaziglyoxime 1 was treated with various aromatic or aliphatic isocyanates to give diazioxalimides 2 a high yield. Diazioxalimides 2 reacted with Ph3P to produce the iminophosphoranes 4; the reaction was directly heated from room temperature to 115 ℃ to get the desired diamino derivatives of bis-1,2,4-oxadiazole 4 in 72-92% yields. In synthesis method II, the same target compounds 4 were synthesized in a one-pot reaction by Ph3P and aromatic or aliphatic isocyanates in toluene for 10 h under 115 ℃ in 53-71% yields. Conclusion: The two procedures provide proficient methods of making nitrogen-containing heterocyclic rings. The structures of target compounds 4 were identified by IR, 1HNMR, 13CNMR and HRMS.

Background: Lymphoma and leukemia, both malignant hematological cancers, are primarily separate diseases, with a majority of cases originating independently. The co-occurrence of lymphoma and leukemia at the time of the first diagnosis is extremely rare, and few relevant reports exist in the medical literature. We describe a case of a patient with non-Hodgkin's lymphoma and acute myeloid leukemia, a very rare occurrence. Case Report: A 57-year-old man complained of fatigue and neck tumors. A physical examination revealed several enlarged superficial lymph nodes throughout the body. On admission, routine blood tests revealed anemia, thrombocytopenia, and normal counts of white blood cells. Cytology of two cervical lymph nodes indicated non- Hodgkin's lymphoma, 18F-PET/CT: multiple enlarged lymph nodes with hypermetabolism, diffuse hypermetabolism of the bone marrow, suggesting lymphoma infiltration in the bone marrow, and a bone marrow biopsy revealed acute myeloid leukemia. Ultimately, the patient was diagnosed with non-Hodgkin’s lymphoma and acute myeloid leukemia. Conclusion: Primary bilineage hematological malignancies are rare, and the mechanism underlying their incidence is unknown. Infiltration of the bone marrow by lymphoma or leukemia can result in diffuse hypermetabolism, which is mostly diagnosed via bone marrow biopsy.