Nanopore sequencing of forensic short tandem repeats using QNome of Qitan Technology.

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs.

Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

The Latest Research Progress on Cell-Free DNA and Prospects of Its Forensic Application.

In recent years, with the continuous progress of DNA extraction and detection technology, cell-free DNA(cfDNA)has been widely used in the life science field, and its potential application value in forensic identification is becoming more and more obvious. This paper reviews the concept, formation mechanism, and classification of cfDNA, etc., and describes the latest research progress of cfDNA in personal identification of crime scene touch DNA samples and non-invasive prenatal paternity testing (NIPPT). Meanwhile, this paper summarizes the potential application of cfDNA in injury inference, and discusses the advantages and disadvantages of common cfDNA analysis methods and techniques, and its application prospects, to provide a new idea for the wide application of cfDNA in the field of forensic science.

Sugars and sucrose transporters in pollinia of Phalaenopsis aphrodite (Orchidaceae).

The pollen grains of Phalaenopsis orchids are clumped tightly together, packed in pollen dispersal units called pollinia. In this study, the morphology, cytology, biochemistry, and sucrose transporters in pollinia of Phalaenopsis orchids were investigated. Histochemical detection was used to characterize the distribution of sugars and callose at the different development stages of pollinia. Ultra-performance liquid chromatography-high resolution-tandem mass spectrometry data indicated that P. aphrodite accumulated abundant saccharides such as sucrose, galactinol, myo-inositol, and glucose, and trace amounts of raffinose and trehalose in mature pollinia. We found that galactinol synthase (PAXXG304680) and trehalose-6-phosphate phosphatase (PAXXG016120) genes were preferentially expressed in mature pollinia. The P. aphrodite genome was identified as having 11 sucrose transporters (SUTs). Our qRT-PCR confirmed that two SUTs (PAXXG030250 and PAXXG195390) were preferentially expressed in the pollinia. Pollinia germinated in pollen germination media (PGM) supplemented with 10% sucrose showed increased callose production and enhanced pollinia germination, but there was no callose or germination in PGM without sucrose. We show that P. aphrodite accumulates high levels of sugars in mature pollinia, providing nutrients and enhanced SUT gene expression for pollinia germination and tube growth.

Response predictor for pigment reduction after one session of photo-based therapy using convolutional neural network: A proof of concept study.

BACKGROUND: Identifying treatment responders after a single session of photo-based procedure for hyperpigmentary disorders may be difficult. OBJECTIVES: We aim to train a convolutional neural network (CNN) to test the hypothesis that there exist discernible features in pretreatment photographs for identifying favorable responses after photo-based treatments for facial hyperpigmentation and develop a clinically applicable algorithm to predict treatment outcome. METHODS: Two hundred and sixty-four sets of pretreatment photographs of subjects receiving photo-based treatment for esthetic enhancement were obtained using the VISIA® skin analysis system. Preprocessing was done by masking the facial features of the photographs. Each set of photographs consists of five types of images. Five independently trained CNNs based on the Resnet50 backbone were developed based on these images and the results of these CNNs were combined to obtain the final result. RESULTS: The developed CNN algorithm has a prediction accuracy approaching 78.5% with area under the receiver operating characteristic curve being 0.839. CONCLUSION: The treatment efficacy of photo-based therapies on facial skin pigmentation can be predicted based on pretreatment images.

Effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

AIM: To investigate the effectiveness of internet-based self-management interventions on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Eight electronic databases including PubMed, Web of Science, Cochrane library, Embase, CINAHL, China National Knowledge Infrastructure, Wangfang and Weipu databases were systematically searched from inception of the database to January 10, 2022. METHODS: Statistical analysis was performed using Review Manager 5.4 and results were reported as mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CI). Outcomes were the forced expiratory volume in 1 second (FEV1), forced volume capacity (FVC) and percent of FEV1/FVC. The Cochrane Risk of Bias Tool was used to assess the risk of bias of included studies. The study protocol was not registered. RESULTS: Eight randomized controlled trials (RCTs) including 476 participants met the inclusion criteria and were included in meta-analysis. It was found that internet-based self-management interventions showed a significant improvement in FVC(L), while FEV1 (%), FEV1 (L), FEV1/FVC (%) and FVC (%) did not significantly improve. CONCLUSIONS: Internet-based self-management interventions were effective in improving pulmonary function in patients with COPD, caution should be exercised in interpreting the results. RCTs of higher quality are needed in the future to further demonstrate the effectiveness of the intervention. RELEVANCE TO CLINICAL PRACTICE: It provides evidence for internet-based self-management interventions in improving pulmonary function in patients with COPD. IMPACT: The results suggested that internet-based self-management interventions could improve the pulmonary function in people with COPD. This study provides a promising alternative method for patients with COPD who have difficulty seeking face-to-face self-management interventions, and the intervention can be applied in clinical settings. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Total syntheses of pongaflavone and its natural analogues.

The efficient total synthesis of anti-tumor natural product pongaflavone (1) was described starting from commercially available 2,4-dihydroxyacetophenone (9) via seven steps and in 16% overall yield. Its two natural analogues pongachromene (2) and 7,8-(2",2"-dimethylpyrano)-5,3',4'-trihydroxy-3-methoxyflavone (3) were also synthesized following the similar procedure with the yields of 11% and 18%, respectively. Their preliminary anti-tumor activities were evaluated by the inhibition effect on A549 cells. The result showed that this kind of natural products exhibited different levels of anti-tumor activity. Among them, pongachromene (2) displayed the best anti-tumor activity.

Effect of cryotherapy on paclitaxel-induced peripheral neuropathy of the hand in female breast cancer patients: A prospective self-controlled study.

AIMS: The purpose of this study was to examine the efficacy of cryotherapy with frozen gloves for the prevention of the chemotherapy-induced peripheral neuropathy of the hand. BACKGROUND: Most breast cancer patients receive chemotherapy; consequently, patients frequently experience adverse effects of chemotherapy-induced peripheral neuropathy. METHODS: A quasi-experimental and prospective self-controlled study was conducted. Breast cancer patients wore frozen glove on the dominant hand for 90 min during their weekly treatment with paclitaxel (80 mg/m2 ). Treatment of the dominant hand, the intervention group, was continued for 12 weeks. The non-dominant hand was considered the control group. RESULTS: A total of 22 patients participated in this study, and only one patient did not reach the cumulative dose (960 mg/m2 ). Findings show that the incidences of sensory and motor symptoms of chemotherapy-induced peripheral neuropathies at the following times (Time 1 to Time 4) were significantly lower in the intervention group than in the control group. However, although the incidences of motor symptoms were lower in the experimental group than in the control group, a significant difference was shown only at Time 4. Additionally, both groups of patients reported that their incidence of sensory symptoms were higher than those of motor symptoms. CONCLUSION: Cryotherapy with frozen gloves is useful in reducing both the sensory and motor symptoms of the chemotherapy-induced peripheral neuropathy of the hands.

[Construction of cell factories for production of patchoulol in Saccharomyces cerevisiae].

Patchoulol is an important sesquiterpenoid in the volatile oil of Pogostemon cablin, and is also considered to be the main contributing component to the pharmacological efficacy and fragrance of P. cablin oil, which has antibacterial, antitumor, antioxidant, and other biological activities. Currently, patchoulol and its essential oil blends are in high demand worldwide, but the traditional plant extraction method has many problems such as wasting land and polluting the environment. Therefore, there is an urgent need for a new method to produce patchoulol efficiently and at low cost. To broaden the production method of patchouli and achieve the heterologous production of patchoulol in Saccharomyces cerevisiae, the patchoulol synthase(PS) gene from P. cablin was codon optimized and placed under the inducible strong promoter GAL1 to transfer into the yeast platform strain YTT-T5, thereby obtaining strain PS00 with the production of(4.0±0.3) mg·L~(-1) patchoulol. To improve the conversion rate, this study used protein fusion method to fuse SmFPS gene from Salvia miltiorrhiza with PS gene, leading to increase the yield of patchoulol to(100.9±7.4) mg·L~(-1) by 25-folds. By further optimizing the copy number of the fusion gene, the yield of patchoulol was increased by 90% to(191.1±32.7) mg·L~(-1). By optimizing the fermentation process, the strain was able to achieve a patchouli yield of 2.1 g·L~(-1) in a high-density fermentation system, which was the highest yield so far. This study provides an important basis for the green production of patchoulol.

Outcome after allogeneic hematopoietic stem cell transplantation following Venetoclax-based therapy among AML and MDS patients.

The use of Bcl-2 inhibitor Venetoclax (VEN) combined with hypomethylating agents or chemotherapy has shown efficacy in treating acute myeloid leukemia (AML) as frontline treatment and for relapse, allowing more patients to bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of VEN-based therapy on the prognosis of subsequent allogeneic HSCT remains unknown. We retrospectively collected data from patients who proceeded to allo-HSCT between November 2018 and November 2020 after VEN-based therapy at five transplant centers in Zhejiang Province, China. A total of 39 patients were analyzed. Thirty-one patients were diagnosed with AML (28 de novo, 3 secondary to MDS), 6 with MDS, and 2 with CMML. The majority (74.4%) of patients received VEN-based therapy for the treatment of relapse (38.5%) or refractory disease (35.9%); 5 (12.8%) received it as an initial treatment, and 5 (12.8%) patients who were already in complete remission (CR) received VEN for further consolidation or deep remission before HSCT. Twenty-seven (69.2%) patients were in CR at the time of HSCT. Day + 100 cumulative incidences of grade I-IV acute graft-versus-host disease (aGVHD) and grade II-IV aGVHD were 43.6% and 15.4%, respectively. Of 34 evaluable patients, 6.4% and 25.6% developed chronic GVHD at 1 year and 2 years. The 100-day cytomegalovirus (CMV) reactivation occurred in 76.3% of patients and Epstein-Barr virus (EBV) reactivation occurred in 29.7% of patients. With a median follow-up of 14.7 months, overall survival, progression-free survival, relapse, and non-relapse mortality incidence at 1 year were 75.5%, 61.6%, 16.7%, and 21.7%, respectively. Both univariate and multivariate analysis revealed that relapsed/refractory (R/R) disease was associated with inferior PFS (HR 4.849, 95% CI 1.009-23.30; p = 0.049). Prior poor response to VEN was found to be a significant factor predicting higher risk of relapse (HR 4.37, 95% CI 1.130-16.9; p = 0.033). Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related mortality and toxicity.

Substrate-Dependent Regioselectivity: Pd/PTC Cooperatively Catalyzed Domino Heck/Allylation of Allenamides with α-Carbon of Carbonyl Compounds.

A Pd/phase-transfer catalyst cooperatively catalyzed domino Heck/allylation reaction is first reported, which represents interesting substrate-dependent regioselectivity. Under the same conditions, Ts-protected N-(2-iodophenyl)allenamides produced only linear allylation products, while Cbz, Ac, or Boc-protected N-(2-iodophenyl)allenamides and N-(2-iodobenzoyl)allenamides with various compounds generated branch allylation products with an exocylic C═C bond and two vicinal stereocenters. Up-scale syntheses and diverse fused cyclization transformations of products were then carried out. The enantioselective version for the domino process was studied.

Phylogenetic relationships of Grapsoidea and insights into the higher phylogeny of Brachyuran.

Decapoda is one of the most diverse crustacean orders, and has become an important research subject. However, the phylogenetic relationships among the main lineages of Decapoda remain uncertain, especially in the order Brachyura. Herein, we sequenced the whole mitochondrial genome of V. litterata and constructed a phylogenetic tree to understand its phylogenetic relationships with other species. The results showed that the mitochondrial genome of V. litterata was generally similar to mitogenomes of Metazoa reported in the literature, with a size of 16,247 bp, 37 genes, and a control region. Both AT-skew and GC-skew were negative, indicating more abundant Cs and Ts than Gs and As. The gene arrangement of V. litterata is identical to those of Eriocheir hepuensis, Cyclograpsus granulosus, Hemigrapsus sanguineus, Helicana wuana, and Helice tientsinensis but differs from the pancrustacean ground pattern and typical arrangement of Brachyuran crabs. Phylogenetic reconstruction showed that V. litterata belongs to the Varunidae.

Auricular Acupressure for Improving Sleep Quality in Patients With Lung Cancer: A Systematic Review and Meta-analysis.

This meta-analysis was conducted to systematically evaluate the efficacy and safety of auricular acupressure on sleep quality in patients with lung cancer. Nine articles with a total of 802 patients were retrieved after searching on 11 electronic databases. Results of the meta-analysis showed that auricular acupressure improved sleep score (standard mean difference: -0.80, 95% confidence intervals: -1.30 to -0.30, P = .002) and reduced sleep disturbance rate (risk ratio: 0.65, 95% confidence intervals: 0.51-0.84, P = .001) and sleep medicine usage (risk ratio: 0.26, 95% confidence intervals: 0.11-0.65, P = .004) significantly. Our review suggests that auricular acupressure is effective and relatively safe in improving sleep quality among patients with lung cancer.

Rice transcription factor GAMYB modulates bHLH142 and is homeostatically regulated by TDR during anther tapetal and pollen development.

GIBBERELLIN MYB GENE (GAMYB), UNDEVELOPED TAPETUM1 (UDT1), TDR INTERACTING PROTEIN2 (TIP2/bHLH142), TAPETUM DEGENERATION RETARDATION (TDR), and ETERNAL TAPETUM 1/DELAYED TAPETUM DEGENERATION (EAT1/DTD) are important transcription factors that play a crucial role during pollen development in rice. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a 'hub' in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of the bHLH142 promoter during the early stage of pollen development, while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. Altered expression of these transcription factors highlights that a tight, precise, and coordinated regulation among them is essential for normal pollen development. Most notably, we show that the regulatory pathways of GAMYB and UDT1 rely on bHLH142 in a direct and indirect manner, respectively, and function in different tissues with distinct biological roles during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

Exercise-induced increases of corticosterone contribute to exercise-enhanced adult hippocampal neurogenesis in mice.

Adult hippocampal neurogenesis (AHN) is suppressed by chronic stress. The negative effect of stress is mainly attributed to increased levels of stress hormones (e.g. glucocorticoids, GCs). Exercise enhances AHN, yet it also stimulates GC secretion. To delineate the paradoxical role of GCs, we took the advantage of a unique mouse strain (L/L) which exhibits an inert response to stress-induced secretion of GCs to study the role of GCs in exercise-induced AHN. Our results showed that basal corticosterone (CORT), the main GCs in rodents, levels were similar between the L/L mice and wild-type (WT) mice. However, levels of CORT in the L/L mice were barely altered and significantly lower than those of the WT mice during treadmill running (TR). AHN was enhanced by 4 weeks of TR in the WT mice, but not L/L mice. WT mice that received daily injection of CORT to evoke serum CORT levels similar to those during exercise for 4 weeks did not affect AHN, whereas injection with large amount of CORT inhibited AHN. Taken together, our results indicated that exercise-related elevation of CORT participates in exercise-enhanced AHN. CORT alone is not sufficient to elicit AHN and may inhibit AHN if the levels are high.

Photoredox-Enabled Synthesis of ß-Substituted Pyrroles from Pyrrolidines.

The merger of photoredox-initiated enamine-imine tautomerization and nucleophilic addition processes to access ß-substituted pyrroles from pyrrolidines has been achieved. The significant advantage of this method is suppressing the Friedel-Crafts reaction, which usually occurs between N-aryl pyrrolidines and the highly electrophilic ketoesters. The good functional group tolerance, high atom economy, and high regioselectivity as well as easy handling conditions make it an appealing alternative to synthesize ß-substituted pyrroles.

Proteomic analysis of differentially expressed proteins in the lipopolysaccharide-stimulated hepatopancreas of the freshwater crayfish Procambarus clarkii.

Procambarus clarkii is one of the most important aquatic invertebrates in China and has high commercial value. However, aquaculture has suffered great economic loss due to outbreaks of infectious diseases in P. clarkii. To identify red swamp crayfish related proteins involved in the response to bacterial infection, we analysed immune-related proteins following lipopolysaccharide (LPS) stimulation by quantitative proteomics. The proteome of the hepatopancreas of P. clarkii challenged with LPS and phosphate-buffered saline was analysed to evaluate the immune response. Based on liquid chromatography coupled with tandem mass spectrometry, 16 upregulated and 29 downregulated proteins were identified. A Gene Ontology analysis demonstrated 5 biological process, 11 cellular component, and 6 molecular function subcategories. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the identified proteins were mainly involved in metabolism, phagosome, and ribosome. Real-time quantitative reverse transcription-PCR revealed that eight immune-related genes were upregulated after LPS stimulation compared to the control. Taken together, the data enhance our understanding of the immune response of crayfish to LPS.

The effects of UVB irradiance on vitiligo phototherapy and UVB-induced photocarcinogenesis.

Phototherapy is the most commonly used modality for repigmenting vitiligo. Currently, UVB emitting devices, including narrow-band UVB (NBUVB) and excimer laser/light, are considered as the treatment of choice. While emitting wavelengths at close proximity, excimer lights emit higher irradiance (HI; W/m2 ) compared to NBUVB. Clinical reports have shown that excimer light is more efficacious in treating vitiligo compared to NBUVB, and we demonstrated that irradiance plays a critical role in promoting melanoblasts differentiation. UVB radiation from the sun is closely associated with photocarcinogenesis of the skin. Sunscreens were used to protect the skin by reducing UVB irradiance (low irradiance (LI) UVB). Sunscreen use was associated with skin cancer reduction in clinical trials. Paradoxically, sunscreen use was associated with increased sunburn episodes in the real-world settings. It was shown that UVB-induced sunburn depends on fluence (J/m2 ) but not irradiance of UVB radiation. We investigated the significance of irradiance in the context of UVB-induced carcinogenesis of the skin. For mice receiving equivalent fluence of UVB exposure, the LIUVB-treated mice showed earlier tumor development, larger tumor burden, and more epidermal keratinocytes harboring mutant p53 as compared to their HIUVB-treated counterparts. These results suggested that at equivalent fluence, LIUVB radiation has more photocarcinogenic potential on the skin compared to its HI counterpart. Since development of sunburn with or without sunscreen use indicates that certain threshold of UVB fluence has been received by the skin at LI and HI, respectively, sunburn episodes with sunscreen use (LIUVB) are more damaging to the skin compared to that without sunscreen (HIUVB) application. In summary, since irradiance plays an important role determining the biological effects of UVB radiation on the skin, future related studies should take this critical parameter into consideration.

Increased Peripheral CD137 Expression in a Mouse Model of Permanent Focal Cerebral Ischemia.

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.