p110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway.

As an evolutionarily conserved transcription factor, Cut-like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro-AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1-PDXP-PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.

Lignin-Based Nanoparticles for Combination of Tumor Oxidative Stress Amplification and Reactive Oxygen Species Responsive Drug Release.

In this study, maleic anhydride-modified lignin (LG-M), a ROS-cleavable thioketal (TK) bond, and polyethylene glycol (PEG) were used to synthesize a lignin-based copolymer (LG-M(TK)-PEG). Doxorubicin (DOX) was attached to the ROS-cleavable bond in the LG-M(TK)-PEG for the preparation of the ROS-activatable DOX prodrug (LG-M(TK-DOX)-PEG). Nanoparticles (NPs) with a size of 125.7 ± 3.1 nm were prepared by using LG-M(TK-DOX)-PEG, and they exhibited enhanced uptake by cancer cells compared to free DOX. Notably, the presence of lignin in the nanoparticles could boost ROS production in breast cancer 4T1 cells while showing little effect on L929 normal cells. This selective effect facilitated the specific activation of the DOX prodrug in the tumor microenvironment, resulting in the superior tumor inhibitory effects and enhanced biosafety relative to free DOX. This work demonstrates the potential of the LG-M(TK-DOX)-PEG NPs as an efficient drug delivery system for cancer treatment.

High-performance GeSi/Ge multi-quantum well photodetector on a Ge-buffered Si substrate.

This work demonstrates a high-performance photodetector with a 4-cycle Ge0.86Si0.14/Ge multi-quantum well (MQW) structure grown by reduced pressure chemical vapor deposition techniques on a Ge-buffered Si (100) substrate. At -1 V bias, the dark current density of the fabricated PIN mesa devices is as low as 3 mA/cm2, and the optical responsivities are 0.51 and 0.17 A/W at 1310 and 1550 nm, respectively, corresponding to the cutoff wavelength of 1620 nm. At the same time, the device has good high-power performance and continuous repeatable light response. On the other hand, the temperature coefficient of resistance (TCR) of the device is as high as -5.18%/K, surpassing all commercial thermal detectors. These results indicate that the CMOS-compatible and low-cost Ge0.86Si0.14/Ge multilayer structure is promising for short-wave infrared and uncooled infrared imaging.

Characterization of the biological and transcriptomic landscapes of bone marrow-derived mesenchymal stem cells in patients with multiple myeloma.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) have been acknowledged as the most important stromal cells in the bone marrow (BM) microenvironment for physiologic hematopoiesis and the concomitant hematologic malignancies. However, the systematic and detailed dissection of the biological and transcriptomic signatures of BM-MSCs in multiple myeloma (MM) are largely unknown. METHODS: In this study, we isolated and identified BM-MSCs from 10 primary MM patients and 10 healthy donors (HD). On the one hand, we compared the multifaceted biological characteristics of the indicated two BM-MSCs, including biomarker expression pattern, multilineage differentiation potential, stemness and karyotyping, together with the cellular vitality and immunosuppressive property. On the other hand, we took advantage of RNA-SEQ and bioinformatics analysis to verify the similarities and differences at the transcriptomic level between MM-MSCs and HD-MSCs. RESULTS: As to biological phenotypes and biofunctions, MM-MSCs revealed conservation in immunophenotype, stemness and differentiation towards adipocytes and chondrocytes with HD-MSCs, whereas with impaired osteogenic differentiation potential, cellular vitality and immunosuppressive property. As to transcriptomic properties, MM-MSCs revealed multidimensional alterations in gene expression profiling and genetic variations. CONCLUSIONS: Overall, our date systematic and detailed reflected the multifaceted similarities and variations between MM-MSCs and HD-MSCs both at the cellular and molecular levels, and in particular, the alterations of immunomodulation and cellular viability of MM-MSCs, which wound benefit the further exploration of the pathogenesis and new drug application (NDA) of multiple myeloma from the view of BM-MSCs.

Alterations in gut and genital microbiota associated with gynecological diseases: a systematic review and meta-analysis.

BACKGROUND: Increasing number of studies have demonstrated certain patterns of microbial changes in gynecological diseases; however, the interaction between them remains unclear. To evaluate the consistency or specificity across multiple studies on different gynecological diseases and microbial alterations at different sites of the body (gut and genital tract), we conducted a systematic review and meta-analysis. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library up to December 5, 2022(PROSPERO: CRD42023400205). Eligible studies focused on gynecological diseases in adult women, applied next-generation sequencing on microbiome, and reported outcomes including alpha or beta diversity or relative abundance. The random-effects model on standardized mean difference (SMD) was conducted using the inverse-variance method for alpha diversity indices. RESULTS: Of 3327 unique articles, 87 eligible studies were included. Significant decreases were found in gut microbiome of patients versus controls (observed species SMD=-0.35; 95%CI, -0.62 to -0.09; Shannon index SMD=-0.23; 95%CI, -0.40 to -0.06), whereas significant increases were observed in vaginal microbiome (Chao1 SMD = 1.15; 95%CI, 0.74 to 1.56; Shannon index SMD = 0.51; 95%CI, 0.16 to 0.86). Most studies of different diagnostic categories showed no significant differences in beta diversity. Disease specificity was observed, but almost all the changes were only replicated in three studies, except for the increased Aerococcus in bacterial vaginosis (BV). Patients with major gynecological diseases shared the enrichment of Prevotella and depletion of Lactobacillus, and an overlap in microbes was implied between BV, cervical intraepithelial neoplasia, and cervical cancer. CONCLUSIONS: These findings demonstrated an association between alterations in gut and genital microbiota and gynecological diseases. The most observed results were shared alterations across diseases rather than disease-specific alterations. Therefore, further investigation is required to identify specific biomarkers for diagnosis and treatment in the future.

Isoliensinine activated the Nrf2/GPX4 pathway to inhibit glutamate-induced ferroptosis in HT-22 cells.

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate-induced injury model of mouse hippocampal neurons HT-22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate-induced HT-22 cells. The results showed that ISO inhibited glutamate-induced ferroptosis of neuronal cells through nuclear factor E2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT-22 cells with ISO significantly reduced glutamate-induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long-chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT-22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT-22 cells was increased, and the expression of downstream heme oxygenase-1 protein was upregulated. In summary, ISO protects HT-22 cells from glutamate-induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway.

Identification and Validation of Key Genes Related to Preferred Flavour Profiles in Australian Commercial Papaya (Carica papaya L.).

Commercial papaya varieties grown in Australia vary greatly in taste and aroma. Previous profiling has identified undesirable 'off tastes' in existing varieties, discouraging a portion of the population from consuming papayas. Our focus on enhancing preferred flavours led to an exploration of the genetic mechanisms and biosynthesis pathways that underlie these desired taste profiles. To identify genes associated with consumer-preferred flavours, we conducted whole RNA sequencing and de novo genome assembly on papaya varieties RB1 (known for its sweet flavour and floral aroma) and 1B (less favoured due to its bitter taste and musty aroma) at both ripe and unripe stages. In total, 180,368 transcripts were generated, and 118 transcripts related to flavours were differentially expressed between the two varieties at the ripe stage. Five genes (cpBGH3B, cpPFP, cpSUS, cpGES and cpLIS) were validated through qPCR and significantly differentially expressed. These genes are suggested to play key roles in sucrose metabolism and aromatic compound production pathways, holding promise for future selective breeding strategies. Further exploration will involve assessing their potential across broader germplasm and various growth environments.

TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus.

Tripartite motif-containing protein 21 (TRIM21) is involved in signal transduction and antiviral responses through the ubiquitination of protein targets. TRIM21 was reported to be related to the imbalance of host cell homeostasis caused by viral infection. Our studies indicated that H5N1 highly pathogenic avian influenza virus (HPAIV) infection up-regulated TRIM21 expression in A549 cells. Western blot and qPCR results showed that knockdown of TRIM21 alleviated oxidative stress and ferroptosis induced by H5N1 HPAIV and promoted the activation of antioxidant pathways. Co-IP results showed that TRIM21 promoted oxidative stress and ferroptosis by regulating the SQSTM1-NRF2-KEAP1 axis by increasing SQSTM1 K63-linked polyubiquitination under the condition of HPAIV infection. In addition, TRIM21 attenuated the inhibitory effect of antioxidant NAC on HPAIV titers and enhanced the promoting effect of ferroptosis agonist Erastin on HPAIV titers. Our findings provide new insight into the role of TRIM21 in oxidative stress and ferroptosis induced by viral infection.

Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure.

OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.

ZNF460-regulated COMMD7 Promotes Acute Myeloid Leukemia Proliferation Via the NF-κB Signaling Pathway.

Acute myeloid leukemia (AML) is a malignancy of the hematological system, for which there remains an urgent need for new therapeutic and diagnostic targets. COMM domain containing 7 (COMMD7) is a recently-identified oncogene linked to poor prognosis in AML. COMMD7 regulates multiple signaling pathways, including nuclear factor-kappa B (NF-κB) signaling. Here, we report that COMMD7 is highly expressed in the AML cell lines KG1a and U937 and that its inhibition by shRNA reduced proliferation, promoted apoptosis and facilitated cell cycle arrest in the G2/M phase in relation to depression of the NF-κB pathway. Furthermore, zinc finger protein 460 (ZNF460) is overexpressed in AML and regulates COMMD7. We found that knockdown of ZNF460 downregulated the expression of COMMD7 while the NF-κB pathway was also inhibited. In addition, we noticed that knockdown of ZNF460 reduced proliferation and increased apoptosis rate of AML cells and that the cell cycle was blocked in the G2/M phase. In brief, our results revealed a critical effect of the ZNF460-COMMD7-NF-κB axis for the proliferation of AML cells. Therefore, COMMD7 may be a possible therapeutic target for AML.

Treatment of immune thrombocytopenia with hetrombopag olamine tablets in a Kabuki syndrome patient with new KMT2D mutations.

Kabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient's peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not reported before.

Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs). RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs). CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

Systematic Quality Evaluation of Epimedium wushanense T. S. Ying Based on Two Quality Control Standards: Total Flavonoid Glycosides and Epimedin C.

Two quality control standards, total flavonoid glycosides of Epimedii Folium and epimedin C of Epimedii Wushanensis Folium, were used to systematically evaluate the quality of Epimedium wushanense T. S. Ying, so as to provide reference for its germplasm screening and resource utilization. Seven representative populations of E. wushanense covering its main distribution areas were uniformly sampled during the flowering period. There were significant quality differences among the populations of E. wushanense. According to the quality standard of total flavonoid glycosides, all populations were superior to the quality standard of the Chinese Pharmacopoeia for Epimedii Folium, with more than 1.5 % total flavonoid glycosides. The variation ranges of epimedin A, epimedin B, epimedin C, icariin and total flavonoid glycosides were 0.40-0.76 %, 0.51-0.83 %, 1.70-9.31 %, 0.40-1.23 % and 3.05-10.61 %, respectively. According to the quality standard of epimedin C, all populations were better than the quality standard of the Chinese Pharmacopoeia for Epimedii Wushanensis Folium, with more than 1.0 % epimedin C. The variation range of epimedin C was 2.22-10.06 %. When comparing the results of the two methods, a trend of slightly lower mean values was found for total flavonoid glycosides, except for the HBXW population. The quality of E. wushanense was superior to both the quality standard of Epimedii Folium and Epimedii Wushanense Folium in the Chinese Pharmacopoeia. Epimedin C was the most abundant component. Among the investigated populations, HBXW and HBGK exhibited the highest quality, and may provide excellent genetic resources for standardized cultivation. In addition, the habitat of these populations can also serve a reference for cultivation conditions.

The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.

The key roles of organelles and ferroptosis in Alzheimer's disease.

Alzheimer's disease (AD), an age-related neurodegenerative disease, is a striking global health problem. Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation products and the accumulation of lethal reactive oxygen species. Strict regulation of iron metabolism is essential to ensure neuronal homeostasis. Excess and deficiency of iron are both associated with neurodegeneration. Studies have shown that oxidative stress caused by cerebral iron metabolism disorders in the body is involved in the process of AD, ferroptosis may play an important role in the pathogenesis of AD, and regulating ferroptosis is expected to be a new direction for the treatment of AD. Various organelles are closely related to ferroptosis: mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome are involved in the regulation of ferroptosis from the aspects of iron metabolism and redox imbalance. In this review, the relationship between AD and the dysfunction of organelles (including mitochondria, endoplasmic reticulum, lysosome, and Golgi apparatus) and the role of organelles in ferroptosis of AD were reviewed to provide insights for understanding the relationship between organelles and ferroptosis in AD and the treatment of AD.

Mechano-tunable chiral metasurfaces via colloidal assembly.

Dynamic control of circular polarization in chiral metasurfaces is being used in many photonic applications. However, simple fabrication routes to create chiral materials with considerable and fully tunable chiroptical responses at visible and near-infrared wavelengths are scarce. Here, we describe a scalable bottom-up approach to construct cross-stacked nanoparticle chain arrays that have a circular dichroism of up to 11°. Due to their layered design, the strong superchiral fields of the inter-layer region are accessible to chiral analytes, resulting in a tenfold enhanced sensitivity in a chiral sensing proof-of-concept experiment. In situ restacking and local mechanical compression enables full control over the entire set of circular dichroism characteristics, namely sign, magnitude and spectral position. Strain-induced reconfiguration opens up an intriguing route towards actively controlled pixel arrays using local deformation, which fosters continuous polarization engineering and multi-channel detection.

DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway.

BACKGROUND: DNA methyltransferase 3A (DNMT3A) often mutate on arginine 882 (DNMT3AR882) in acute myeloid leukemia (AML). AML patients with DNMT3A R882 mutation are usually resistant to daunorubicin treatment; however, the associated mechanism is still unclear. Therefore, it is urgent to investigate daunorubicin resistance in AML patients with DNMT3A R882 mutant. METHOD: AML cell lines with DNMT3A-wild type (DNMT3A-WT), and DNMT3A-Arg882His (DNMT3A-R882H) mutation were constructed to investigate the role of DNMT3A R882H mutation on cell proliferation, apoptosis and cells' sensitivity to Danunorubin. Bioinformatics was used to analyze the role of nuclear factor-E2-related factor (NRF2) in AML patients with DNMT3A R882 mutation. The regulatory mechanism of DNMT3A R882H mutation on NRF2 was studied by Bisulfite Sequencing and CO-IP. NRF2 inhibitor Brusatol (Bru) was used to explore the role of NRF2 in  AML cells carried DNMT3A R882H mutation. RESULTS: AML cells with a DNMT3A R882H mutation showed high proliferative and anti-apoptotic activities. In addition, mutant cells were less sensitive to daunorubicin and had a higher NRF2 expression compared with those in WT cells. Furthermore, the NRF2/NQO1 pathway was activated in mutant cells in response to daunorubicin treatment. DNMT3A R882H mutation regulated the expression of NRF2 via influencing protein stability rather than decreasing methylation of NRF2 promoter. Also, NRF2/NQO1 pathway inhibition improved mutant cells' sensitivity to daunorubicin significantly. CONCLUSION: Our findings identified NRF2 as an important player in the regulation of cell apoptosis through which helps mediate chemoresistance to daunorubicin in AML cells with DNMT3A R882H mutation. Targeting NRF2 might be a novel therapeutic approach to treat AML patients with a DNMT3A R882H mutation. Video abstract.

The roles of primary care doctors in the COVID-19 pandemic: consistency and influencing factors of doctor's perception and actions and nominal definitions.

BACKGROUND: At the end of 2019, the Coronavirus Disease 2019 (COVID-19) pandemic broke out. As front-line health professionals, primary care doctors play a significant role in screening SARS-CoV-2 infection and transferring suspected cases. However, the performance of primary care doctors is influenced by their knowledge and role perception. A web-based cross-sectional survey was conducted to assess the consistency and influencing factors of primary care doctor's role perception and expert advice in the guidelines (regulatory definition). METHODS: We designed the questionnaire using "Wenjuanxing" platform, distributed and collected the questionnaire through WeChat social platform, and surveyed 1758 primary care doctors from 11 community health service stations, community health service centers and primary hospitals in Zhejiang Province, China. After the questionnaire was collected, descriptive statistics were made on the characteristics of participants, and univariate analysis and multivariate analysis were used to determine the relevant factors affecting their role cognition. RESULTS: In the reporting and referral suspected cases and patients receiving treatment, most participants' cognition of their roles were consistent with the requirements of guidelines. However, 49.54% and 61.43% of participant doctors were not in line with the government guidelines for diagnosing and classifying COVID-19 and treating suspected cases, respectively. Having a middle or senior professional title and participating in front-line COVID-19 prevention and control work is beneficial to the accurate role perception of diagnosis and classification of COVID-19, the reporting and transfer of suspected cases, and the treatment of suspected cases. CONCLUSIONS: Primary care doctors' role perceptions in the COVID-19 pandemic are not always consistent with government guidelines in some aspects, such as transferring and diagnosing suspected cases. Therefore, it is essential to guide primary care doctors in performing their duties, especially those with lower professional titles.

First Report of Crown and Root Rot Caused by Phytopythium helicoides on Photinia × fraseri Dress in China.

Photinia × fraseri Dress is a hybrid species of Rosaceae and Photinia genus which is widely cultivated in China. During 2020 and 2021, approximately 80% of plants growing in Xuanwu district of Nanjing, China, exhibited disease symptoms including blight, necrosis, and dieback of crowns and roots. Symptomatic root tissues collected from 2-year-old plants were rinsed with water, cut into 2-mm tissues which were surface-sterilized in 70% ethanol for 60 s, and plated onto 10% V8 PARP agar and incubated in the dark at 26°C for 3 days. Hyphae emerged from 70% of the samples. Two representative isolates (PF-he2, PF-he3) were obtained and deposited. Ten agar plugs (2×2 mm2) of each isolate were transferred into 10 mL of 10% V8 juice to produce mycelial mats. To stimulate sporangial production, 3-5 drops of soil extract solution (soil collected from healthy fields, immersed in sterile water, and filtered) were added to each plate. Sporangia were terminal, ovoid to globose or papillate. The zoospores were 7.1-9.3 µm in diameter. Each oogonium contained a single, smooth, spherical and aplerotic oospore with a diameter of 24.5-32.6 µm. These morphological properties resemble those of Phytopythium helicoides (CBS286.31 from S. F. Ashby). For molecular identification, the large subunit (LSU) rDNA, cytochrome c oxidase I (COXI) gene, and COXII gene were amplified using the primer pairs NL1/NL4 , FM55/FM52R , and FM66/FM58 . The LSU, COXI, and COXII sequences of isolate PF-he2 were 100% (763/763 nt), 98.07% (1066/1087 nt), 99.64% (561/563 nt) identical to isolate CBS 286.31 (AY598665.2), GDGJ6 (KT750956.1), and TC3 (MN952224.1), respectively. Based on the morphological and molecular analysis, the two isolates shared 100% homology were identified as Phytopythium helicoides. The pathogenicity of two isolates were tested on potted 2-yr-old (40-cm tall) P. × fraseri. Six plants were dug up to expose root balls which were wounded before inoculations with a sterile needle, and then inoculated with zoospore suspension (106 zoospore/mL). Controls were treated with ddH2O. Three seedlings/isolate were used for each treatment including controls. All plants were repotted using the original sterilized potting mix and pots. After inoculation, the plants were covered with plastic bags, and sterilized H2O was sprayed into the bags twice per day to maintain humidity and kept in a greenhouse at the day/night temperatures at 25/16 °C. All the inoculated plants showed lesions similar to those observed in the field after 23 days , whereas controls were asymptomatic. The isolates were reisolated from the lesions and sequenced as P. helicoides which has found causing root rot on Nelumbo nucifera, Rhododendron pulchrum, Zea mays in China, and also on Fragaria × ananassa in America, Peach Rootstock in California. Globally, this is the first report of P. helicoides causing crown blight and root rot of P. × fraseri. Management programs are under development to contain the spread of P. helicoides and treat diseased plants.

Biochemical, Sensory, and Molecular Evaluation of Flavour and Consumer Acceptability in Australian Papaya (Carica papaya L.) Varieties.

Inconsistency in flavour is one of the major challenges to the Australian papaya industry. However, objectively measurable standards of the compound profiles that provide preferable taste and aroma, together with consumer acceptability, have not been set. In this study, three red-flesh papayas (i.e., 'RB1', 'RB4', and 'Skybury') and two yellow-flesh papayas (i.e., '1B' and 'H13') were presented to a trained sensory panel and a consumer panel to assess sensory profiles and liking. The papaya samples were also examined for sugar components, total soluble solids, and 14 selected volatile compounds. Additionally, the expression patterns of 10 genes related to sweetness and volatile metabolism were assessed. In general, red papaya varieties had higher sugar content and tasted sweeter than yellow varieties, while yellow varieties had higher concentrations of citrus floral aroma volatiles and higher aroma intensity. Higher concentrations of glucose, linalool oxide, and terpinolene were significantly associated with decreased consumer liking. Significant differences were observed in the expression profiles of all the genes assessed among the selected papaya varieties. Of these, cpGPT2 and cpBGLU31 were positively correlated to glucose production and were expressed significantly higher in '1B' than in 'RB1' or 'Skybury'. These findings will assist in the strategic selective breeding for papaya to better match consumer and, hence, market demand.