A Novel Ectodysplasin a Gene mutation of X-Linked Hypohidrotic Ectodermal Dysplasia.

Introduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings. Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay. Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent. Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.

Case report: Disseminated mucormycosis misdiagnosed as malignancy developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus following SARS-CoV-2 infection in a woman.

Mucormycosis has become more prevalent during the COVID-19 pandemic and is associated with a high mortality rate. However, concurrent host allergic reactions, invasive pulmonary mucormycosis, and disseminated mucormycosis are rarely reported. Herein, we describe a case of disseminated mucormycosis initially misdiagnosed as a malignancy that developed from allergic bronchopulmonary mycosis caused by Rhizopus microsporus in a woman with post-SARS-CoV-2 infection. The previously healthy patient presented with a sizeable mass in the right middle lobe and multiple lesions across the lungs, brain, spleen, kidneys, pancreas, and subcutaneous tissue 6 months after SARS-CoV-2 infection, mimicking an extensive metastatic malignancy. Eosinophilia, elevated total plasma immunoglobulin E, and significant eosinophilic lung tissue infiltration were observed. Rhizopus microsporus was isolated from subcutaneous tissue, and hyphae were detected in the lung tissue. Sequential amphotericin B liposomes followed by isavuconazole antifungal therapy combined with systemic corticosteroids improved symptoms, significantly reduced the sizes of pulmonary lesions, and reduced eosinophil count. However, it failed to halt the overall progression of the disease, and the patient died. The absence of asthma-like symptoms and delayed recognition of invasive fungal infection signs contributed to poorer outcomes, highlighting the need for a thorough post-COVID-19 follow-up.

Combining multimodal diffusion-weighted imaging and morphological parameters for detecting lymph node metastasis in cervical cancer.

BACKGROUND: Accurate detection of lymph node metastasis (LNM) is crucial for determining the tumor stage, selecting optimal treatment, and estimating the prognosis for cervical cancer. This study aimed to assess the diagnostic efficacy of multimodal diffusion-weighted imaging (DWI) and morphological parameters alone or in combination, for detecting LNM in cervical cancer. METHODS: In this prospective study, we enrolled consecutive cervical cancer patients who received multimodal DWI (conventional DWI, intravoxel incoherent motion DWI, and diffusion kurtosis imaging) before treatment from June 2022 to June 2023. The largest lymph node (LN) observed on each side on imaging was matched with that detected on pathology to improve the accuracy of LN matching. Comparison of the diffusion and morphological parameters of LNs and the primary tumor between the positive and negative LN groups. A combined diagnostic model was constructed using multivariate logistic regression, and the diagnostic performance was evaluated using receiver operating characteristic curves. RESULTS: A total of 93 cervical cancer patients were enrolled: 35 with LNM (48 positive LNs were collected), and 58 without LNM (116 negative LNs were collected). The area under the curve (AUC) values for the apparent diffusion coefficient, diffusion coefficient, mean diffusivity, mean kurtosis, long-axis diameter, short-axis diameter of LNs, and the largest primary tumor diameter were 0.716, 0.720, 0.716, 0.723, 0.726, 0.798, and 0.744, respectively. Independent risk factors included the diffusion coefficient, mean kurtosis, short-axis diameter of LNs, and the largest primary tumor diameter. The AUC value of the combined model based on the independent risk factors was 0.920, superior to the AUC values of all the parameters mentioned above. CONCLUSION: Combining multimodal DWI and morphological parameters improved the diagnostic efficacy for detecting cervical cancer LNM than using either alone.

BNIP3-mediated mitophagy boosts the competitive growth of Lenvatinib-resistant cells via energy metabolism reprogramming in HCC.

An increasing evidence supports that cell competition, a vital selection and quality control mechanism in multicellular organisms, is involved in tumorigenesis and development; however, the mechanistic contributions to the association between cell competition and tumor drug resistance remain ill-defined. In our study, based on a contructed lenvitinib-resistant hepatocellular carcinoma (HCC) cells display obvious competitive growth dominance over sensitive cells through reprogramming energy metabolism. Mechanistically, the hyperactivation of BCL2 interacting protein3 (BNIP3) -mediated mitophagy in lenvatinib-resistant HCC cells promotes glycolytic flux via shifting energy production from mitochondrial oxidative phosphorylation to glycolysis, by regulating AMP-activated protein kinase (AMPK) -enolase 2 (ENO2) signaling, which perpetually maintaining lenvatinib-resistant HCC cells' competitive advantage over sensitive HCC cells. Of note, BNIP3 inhibition significantly sensitized the anti-tumor efficacy of lenvatinib in HCC. Our findings emphasize a vital role for BNIP3-AMPK-ENO2 signaling in maintaining the competitive outcome of lenvitinib-resistant HCC cells via regulating energy metabolism reprogramming; meanwhile, this work recognizes BNIP3 as a promising target to overcome HCC drug resistance.

The neurocognitive processing mechanism of English subject-verb agreement by Chinese-speaking learners.

Determiner phrases (DPs), an overarching term, can be classified into two determiner types: referential determiner phrases (RDPs, e.g., the boy) and quantificational determiner phrases (QDPs, e.g., each boy). Using the event-related potential (ERP) technique, this study explored the modulation of RDP vs. QDP in the online processing of English subject-verb agreement with omission errors by Chinese learners of English, addressing the question of whether singular quantification increases or decreases Chinese learners' sensitivity to agreement violations. The experiment manipulated the determiner type, specifically RDP vs. QDP, and grammaticality (grammatical vs. ungrammatical). The results indicated that similar to previous studies, a P600 effect was elicited in response to subject-verb agreement violations with omission errors, demonstrating that Chinese L2 learners are sensitive to such agreement violations. Additionally, the ERP patterns exhibited variations due to D-linking and number specification of RDP and QDP. Regarding D-linking, subject-verb agreement violations in the QDP conditions, necessitating integration of discourse-related knowledge, elicited laterally and frontally distributed P600 effects associated with integration complexity at the discourse level; however, non-D-linked referential determiners elicited the posteriorly-distributed P600 effects. Differences in number specification resulted in the distinctive P600 latencies and whether P600 was preceded by N400 or not. While both the RDP and QDP conditions exhibited the P600 effects, the onset latency of this effect in the number-unspecified RDP condition was 300 ms later compared to the number-specified QDP condition. Furthermore, an additional N400 component observed in the RDP condition suggests that L2 learners acquire morphologically complex subject-verb agreements by rote, treating them as unanalyzed chunks. This N400 component was absent in the QDP condition. From these results, the conclusion can be drawn that L2 learners are sensitive to the subject-verb agreement violations with omission errors, and L2 processing patterns of subject-verb agreement vary with different features of determiners, providing further evidence for the cue-based retrieval model during comprehension of grammatical sentences. Pedagogical implications are provided, and the future research direction is suggested.

Sulfate-reducing consortium HQ23 stabilizes metal(loid)s and activates biological N-fixation in mixed heavy metal-contaminated soil.

Sulfate-reducing bacteria (SRB) are used in the remediation of mine pollution; however, the mechanism of stabilizing multiple heavy metal(loid)s by the SRB consortium under low oxygen conditions needs further study. Indigenous microflora were extracted from non-ferrous metal-contaminated soil co-inoculated with enriched SRB consortium and assembled as the HQ23 consortium. The presence of Desulfovibrio (SRB) in HQ23 was confirmed by 16S rRNA sequencing and qPCR. The effects of culture media, dissolved oxygen (DO), SO42¯, and pH on the HQ23 growth rate, and the SO42¯-reducing activity were examined. Data indicates that the HQ23 sustained SRB function under low DO conditions (3.67 ± 0.1 mg/L), but the SRB activity was inhibited at high DO content (5.75 ± 0.39 mg/L). The HQ23 can grow from pH 5 to pH 9 and can decrease mobile or bioavailable Cr, Cu, and Zn concentrations in contaminated soil samples. FTIR revealed that Cu and Cr adsorbed to similar binding sites on bacteria, likely decreasing bacterial Cu toxicity. Increased abundances of DSV (marker for Desulfovibrio) and nifH (N-fixation) genes were observed, as well as an accumulation of nitrate-N content in soils suggesting that HQ23 stimulates the biological N-fixation in soils. This study strongly supports the future application of SRB for the bioremediation of heavy metal-polluted sites.

Detoxification of phoxim by a gut bacterium of Delia antiqua.

The presence of certain associated bacteria has been reported to increase pest resistance to pesticides, which poses a serious threat to food security and the environment. Researches on the above microbe-derived pesticide resistance would bring innovative approaches for pest management. Investigations into the phoxim resistance of Delia antiqua, one Liliaceae crop pests, revealed the contribution of a phoxim-degrading gut bacterium, D39, to this resistance. However, how the strain degraded phoxim was unknown. In this study, the role of D39 in phoxim degradation and resistance was first confirmed. DT, which had an identical taxonomy but lacked phoxim-degrading activity, was analyzed alongside D39 via comparative genomics to identify the potential phoxim degrading genes. In addition, degradation metabolites were identified, and a potential degradation pathway was proposed. Furthermore, the main gene responsible for degradation and the metabolites of phoxim were further validated via prokaryotic expression. The results showed that D39 contributed to resistance in D. antiqua larva by degrading phoxim. Phoxim was degraded by an enzyme encoded by the novel gene phoD in D39 to O,O-diethyl hydrogen phosphorothioate and 2-hydroxyimino-2-phenylacetonitrile. Finally, downstream products were metabolized in the tricarboxylic acid cycle. Further analysis via prokaryotic expression of phoD confirmed its degradation activity. The mechanisms through which gut microbes promote pesticide resistance are elucidated in this study. These results could aid in the development of innovative pest control methods. In addition, this information could also be used to identify microbial agents that could be applied for the remediation of pesticide contamination.

An Investigation of the Magnitude of the Role of Different Plant Species in Grassland Communities on Species Diversity, China.

In this study, we selected four grassland plots in Altai forest area and used the field survey method of "two-valued occurrence" to obtain the occurrence data of each plant species in the plots so as to calculate the species diversity index value of the community as a whole and the species diversity index value of each plant species not present in the community and to make use of the difference between these two diversity indices to determine the role of each plant species in the overall species diversity of the community. The difference between these two diversity indices was used to investigate the role of each plant species in the overall species diversity of the community. The results show the following: (1) In the grassland of the Altai forest area in Xinjiang, Asteraceae, Poaceae, Fabaceae, Polygonaceae, and Rosaceae are the dominant families, among which the genera Puccinellia Parl, Taraxacum, Pharbitis, Lactuca, Geranium, and Alchemilla are the dominant genera. (2) The plant species with the greatest contribution to species diversity in the four grassland samples was not the first dominant species of the community, but rather the plant species whose dominance was in the second to sixth position. (3) The first dominant species was overwhelmingly dominant in the four sample plots, and it served to increase the overall diversity of the community. (4) The overall trend in the size of the role of species in diversity is unimodal, i.e., logarithmically increasing to a maximum as species dominance decreases and then exponentially or linearly decreasing and eventually converging to zero. The synthesis showed that it was not the first dominant species that played the largest role in species diversity in the different grassland communities and that the overwhelmingly dominant species reduced the species diversity of the community.

Transcription factor binding site divergence across maize inbred lines drives transcriptional and phenotypic variation.

Regulatory elements are important constituents of plant genomes that have shaped ancient and modern crops. Their identification, function, and diversity in crop genomes however are poorly characterized, thus limiting our ability to harness their power for further agricultural advances using induced or natural variation. Here, we use DNA affinity purification-sequencing (DAP-seq) to map transcription factor (TF) binding events for 200 maize TFs belonging to 30 distinct families and heterodimer pairs in two distinct inbred lines historically used for maize hybrid plant production, providing empirical binding site annotation for 5.3% of the maize genome. TF binding site comparison in B73 and Mo17 inbreds reveals widespread differences, driven largely by structural variation, that correlate with gene expression changes. TF binding site presence-absence variation helps clarify complex QTL such as vgt1, an important determinant of maize flowering time, and DICE, a distal enhancer involved in herbivore resistance. Modification of TF binding regions via CRISPR-Cas9 mediated editing alters target gene expression and phenotype. Our functional catalog of maize TF binding events enables collective and comparative TF binding analysis, and highlights its value for agricultural improvement.

Discovery and engineering of ChCas12b for precise genome editing.

Many clustered regularly interspaced short palindromic repeat and CRISPR-associated protein 12b (CRISPR-Cas12b) nucleases have been computationally identified, yet their potential for genome editing remains largely unexplored. In this study, we conducted a GFP-activation assay screening 13 Cas12b nucleases for mammalian genome editing, identifying five active candidates. Candidatus hydrogenedentes Cas12b (ChCas12b) was found to recognize a straightforward WTN (W = T or A) proto-spacer adjacent motif (PAM), thereby dramatically expanding the targeting scope. Upon optimization of the single guide RNA (sgRNA) scaffold, ChCas12b exhibited activity comparable to SpCas9 across a panel of nine endogenous loci. Additionally, we identified nine mutations enhancing ChCas12b specificity. More importantly, we demonstrated that both ChCas12b and its high-fidelity variant, ChCas12b-D496A, enabled allele-specific disruption of genes harboring single nucleotide polymorphisms (SNPs). These data position ChCas12b and its high-fidelity counterparts as promising tools for both fundamental research and therapeutic applications.

Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.

Low glucose is a common microenvironment for rapidly growing solid tumors, which has developed multiple approaches to survive under glucose deprivation. However, the specific regulatory mechanism remains largely elusive. In this study, we demonstrate that glucose deprivation, while not amino acid or serum starvation, transactivates the expression of DCAF1. This enhances the K48-linked polyubiquitination and proteasome-dependent degradation of Rheb, inhibits mTORC1 activity, induces autophagy, and facilitates cancer cell survival under glucose deprivation conditions. This study identified DCAF1 as a new cellular glucose sensor and uncovered new insights into mechanism of DCAF1-mediated inactivation of Rheb-mTORC1 pathway for promoting cancer cell survival in response to glucose deprivation.

ERCC3-Related Genes May Aid in the Prognostic and Immunotherapeutic Analysis of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has high morbidity and mortality worldwide. Excision repair cross-complement 3 (ERCC3), a key functional gene in the nucleotide excision repair (NER) pathway, is commonly mutated or overexpressed in cancers and is thought to be a key gene contributing to the development of HCC. The characteristics of immune cell infiltration in the global tumor microenvironment (TME) mediated by ERCC3 and its related key genes in HCC are still unclear. The aim of this study was to integrate the role of ERCC3-related key genes in assessing the TME cell infiltration characteristics, immunotherapy efficacy, and prognosis of HCC patients. This study provides a theoretical basis for the study of immunological mechanisms and prognosis prediction in HCC. METHODS: The HCC cohort from the TCGA database included 50 normal samples and 374 tumor samples to compare the differences in ERCC3-related gene expression and prognosis between liver tumor tissues and normal liver tissues and to analyze the extent to which different genes infiltrated TME cells by quantifying the relative abundance of 24 cells through single-sample genome enrichment analysis (ssGSEA). A risk score associated with the ERCC3 gene was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. RESULTS: The expression of 11 ERCC3-related genes was significantly upregulated in HCC tumor tissues compared to normal liver tissues, and high expression of these genes was significantly associated with poor prognosis in HCC patients. The key genes (11 ERCC3-related genes) were closely associated with the nucleic acid reduction signaling pathway in nucleic acid metabolism and the viral oncogenic pathway, suggesting that these key genes may play a role in tumor cell proliferation, migration, and invasion, as well as in the pathogenesis of virus-associated HCC. In addition, the infiltration characteristics of TME immune cells in normal and tumor tissues were different. Immune and mesenchymal activity was significantly lower in tumor tissues than in healthy liver tissues. This study revealed that key genes were significantly positively correlated with CTLA4 and enriched in central memory CD4 T cells, effector memory CD4 T cells, activated CD4 T cells, and type 2 T helper cells. The prognostic model constructed by regression analysis could better distinguish patients into high-risk and low-risk groups, and the survival analysis showed that the survival time of patients with high-risk score subtypes was significantly lower than that of patients with low-risk scores and that the high-risk group contained higher levels of immune-suppressive cells, which may be a mediator of immune escape. Moreover, multivariate analyses showed that the risk score profile is a reliable and unbiased biomarker for assessing the prognosis of HCC patients, and its value in predicting the outcome of immunotherapy was also confirmed. CONCLUSION: This study revealed a novel genetic signature that is significantly associated with TME cell infiltration and prognosis in HCC patients. It demonstrated that the combined action of multiple key genes associated with ERCC3 plays a crucial role in shaping the diversity and complexity of TME cell infiltrates. Evaluating the combined characteristics of multiple key genes associated with ERCC3 can help predict the outcome of immunotherapy in patients and provide new potential targets for immuno-individualized therapeutic studies on HCC.

Characterization of VOCs emissions and associated health risks inherent to the packaging and printing industries in Shandong Province, China.

Comprehensive volatile organic compounds (VOCs) emission control is imperative to decreasing occupational health risks and environmental impact of the packaging and printing industries. In this work, we investigated the VOCs emission characteristics and concentrations of individual contaminants generated by the packaging and printing industries, with regard to various categories, processes, and geographic regions. VOCs emissions, ozone formation potential (OFP), and associated health risks were assessed at 10 representative packaging and printing firms across several cities in Shandong Province, China. Plastic packaging enterprises had the greatest levels of unorganized VOCs emissions, consisting predominantly of oxygenated volatile organic compounds (OVOCs), followed by alkanes and halocarbons. From metal and paper packaging enterprises, OVOCs, alkanes, and aromatics were significant components of unorganized VOCs emissions. Aromatics, halocarbons, and OVOCs contributed significantly to OFP in workshops. The potential carcinogenic risk associated with VOCs in the packaging and printing industries was not significant. However, according to the findings in this study, the workshop environment may provide a comparatively elevated non-carcinogenic risk attributable to ethyl acetate, isopropanol, acrolein, 1,1,2-Trichloroethane, 1,2-Dichloropropane, and naphthalene exposure. In particular, the endocrine-disrupting and genetic toxic effects caused by benzene, toluene, styrene, and naphthalene should not be overlooked. Thus, it is essential to provide precedence to the working environment conditions of workshop laborers, while also undertaking scientific and systematic measures to mitigate the detrimental impacts of VOCs on the environment and human welfare.

Treatment experience for different risk groups of Kaposiform hemangioendothelioma.

Background: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging. Objective: The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE. Methods: Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data. Results: In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge. Conclusions: Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Grass carp (Ctenopharyngodon idella) NIK up-regulates the expression of IL-8 by activating the NF-κB canonical pathway.

NIK (NF-κB inducing kinase) belongs to the mitogen-activated protein kinase family, which activates NF-κB and plays a vital role in immunology, inflammation, apoptosis, and a series of pathological responses. In NF-κB noncanonical pathway, NIK and IKKα have been often studied in mammals and zebrafish. However, few have explored the relationship between NIK and other subunits of the IKK complex. As a classic kinase in the NF-κB canonical pathway, IKKß has never been researched with NIK in fish. In this paper, the full-length cDNA sequence of grass carp (Ctenopharyngodon idella) NIK (CiNIK) was first cloned and identified. The expression level of CiNIK in grass carp cells was increased under GCRV stimuli. Under the stimulation of GCRV, poly (I:C), and LPS, the expression of NIK in various tissues of grass carp was also increased. This suggests that CiNIK responds to viral stimuli. To study the relationship between CiNIK and CiIKKß, we co-transfected CiNIK-FLAG and CiIKKB-GFP into grass carp cells in coimmunoprecipitation and immunofluorescence experiments. The results revealed that CiNIK interacts with CiIKKß. Besides, the degree of autophosphorylation of CiNIK was enhanced under poly (I:C) stimulation. CiIKKß was phosphorylated by CiNIK and then activated the activity of p65. The activity change of p65 indicates that NF-κB downstream inflammatory genes will be functioning. CiNIK or CiIKKß up-regulated the expression of IL-8. It got higher when CiNIK and CiIKKß coexisted. This paper revealed that NF-κB canonical pathway and noncanonical pathway are not completely separated in generating benefits.

Tat-dependent conditionally replicating adenoviruses expressing diphtheria toxin A for specifically killing HIV-1-infected cells.

HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effects and drive the emergence of drug-resistant HIV-1 variants. Gene therapy represents an alternative approach to overcome the limitations of conventional treatments against HIV-1 infection. In this study, we constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus, which selectively replicates and expresses the diphtheria toxin A chain (Tat-CRAds-DTA) in HIV-1-infected cells both in vitro and in vivo. We found that Tat-CRAds-DTA could specifically induce cell death and inhibit virus replication in HIV-1-infected cells mediated by adenovirus proliferation and DTA expression. A low titer of progeny Tat-CRAds-DTA was also detected in HIV-1-infected cells. In addition, Tat-CRAds-DTA showed no apparent cytotoxicity to HIV-1-negative cells and demonstrated significant therapeutic efficacy against HIV-1 infection in a humanized mouse model. The findings in this study highlight the potential of Tat-CRAds-DTA as a new gene therapy for the treatment of HIV-1 infection.

Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of Chinese Assam tea (Camellia sinensis var. assamica).

Chinese Assam tea (Camellia sinensis var. assamica) is an important tea crop with a long history of cultivation in Yunnan, China. Despite its potential value as a genetic resource, its genetic diversity and domestication/breeding history remain unclear. To address this issue, we genotyped 469 ancient tea plant trees representing 26 C. sinensis var. assamica populations, plus two of its wild relatives (six and three populations of C. taliensis and C. crassicolumna, respectively) using 16 nuclear microsatellite loci. Results showed that Chinese Assam tea has a relatively high, but comparatively lower gene diversity (HS = 0.638) than the wild relative C. crassicolumna (HS = 0.658). Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups, with considerable interspecific introgression. The Chinese Assam tea accessions clustered into three gene pools, corresponding well with their geographic distribution. However, NewHybrids analysis indicated that 68.48% of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene pools. In addition, 10% of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and C. taliensis. Our results suggest that Chinese Assam tea was domesticated separately in three gene pools (Puer, Lincang and Xishuangbanna) in the Mekong River valley and that the hybrids were subsequently selected during the domestication process. Although the domestication history of Chinese Assam tea in southwestern Yunnan remains complex, our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

Factors Influencing the Self-management of Breast Cancer-Related Lymphedema: A Meta-synthesis of Qualitative Studies.

BACKGROUND: Patients with breast cancer have an estimated 14% to 60% risk of developing lymphedema after treatment. Self-management behavior strategies regarding lymphedema are essential in preventing and alleviating the severity of lymphedema. OBJECTIVE: The aim of this study was to evaluate qualitative research evidence on the potential influencing factors for self-management behaviors of lymphedema in patients with breast cancer. METHODS: A systematic search of 10 electronic databases was conducted to identify qualitative studies on patient experience of lymphedema self-management. The following databases were included and appraised using the Joanna Briggs Institute Critical Appraisal Checklist: Cochrane Library, PubMed, EMBASE, Web of Science, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Med Online, and Chinese Biomedical Database. RESULTS: The literature search yielded 5313 studies, of which only 22 qualitative studies fulfilled the eligibility criteria. Five synthesized findings were derived encompassing personal characteristics, personal knowledge and experience, personal health beliefs, self-regulation skills and abilities, and social influences and support. CONCLUSIONS: Patients with breast cancer are confronted with many challenges when performing self-management of lymphedema. Therefore, it is important to recognize potential facilitators and barriers to further offer practical recommendations that promote self-management activities for lymphedema. IMPLICATIONS FOR PRACTICE: Healthcare professionals should receive consistent training on lymphedema management. On the basis of individual patient characteristics, tailored education and support should be provided, including transforming irrational beliefs, and improving related knowledge and skills, with the aim to promote self-management behaviors with respect to lymphedema.

Visible-Light-Induced Regioselective Radical-Polar Crossover 1,4-Hydrophosphinylation of 1,3-Enynes: Access to Trisubstituted Allenes Bearing a Phosphine Oxide Group.

The radical 1,4-functionalizations of 1,3-enynes have emerged as a powerful strategy for the synthesis of multisubstituted allenes. However, the phosphorus-centered radical-initiated transformations remain largely elusive. Herein, visible-light photoredox catalytic regioselective radical hydrophosphinylation of 1,3-enynes with diaryl phosphine oxides as phosphinoyl radical precursors has been realized. This protocol features mild conditions, a wide substrate scope, and good functional group tolerance, producing a diverse range of phosphinoyl-substituted allenes in moderate to good yields with high atom economy. Detailed mechanistic experiments revealed a radical-polar crossover process in the reaction.

A colorimetric and electrochemical dual-mode Hg2+ sensor utilizing oxidase-like activity arising from the combination of Hg2+ and palladium metal-organic framework@graphene.

Developing convenient and reliable methods for Hg2+ monitoring is highly important. Some precious metal nanomaterials with intriguing peroxidase-like activity have been used for highly sensitive Hg2+ detection. However, H2O2 must be added during these detections, which impedes practical applications of Hg2+ sensors due to its susceptible decomposition by environmental factors. Herein, we discovered that the combination of Hg2+ and palladium metal-organic framework@graphene (Pd-MOF@GNs) exhibits oxidase-like activity (OXD). In the absence of H2O2, this activity not only catalyzes the oxidation of chromogenic substrates such as 3,3',5,5'-tetramethylbenzidine (TMB) or o-phenylenediamine (OPD) to produce a color change but also enhances the electrical signals during OPD oxidation. Based on these properties, an effective and convenient dual-mode colorimetric and electrochemical sensor for Hg2+ has been developed. The colorimetric and amperometric linear relationships for Hg2+ were 0.045 µM-0.25 mM and 0.020 µM-2.0 mM, respectively. The proposed strategy shows good recovery in real sample tests, indicating promising prospects for multiple environmental sample detection of Hg2+ without relying on H2O2. The colorimetric and electrochemical dual-mode Hg2+ sensor is expected to hold great potentials in applications such as environmental monitoring, rapid field detection, and integration into smartphone detection of Hg2+.