Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

[Epidemiological and spatial-temporal clustering characteristics of pertussis in Hebei Province from 2013 to 2022].

Objective: To analyze the spatial-temporal epidemiological characteristics of pertussis from 2013 to 2022 in Hebei Province and to provide a reference for improving prevention and control measures. Methods: Based on the data of pertussis reported in Hebei Province during 2013-2022 to analyze the popular characteristic, the ArcGIS 10.8 software was used to construct a ring map and to perform spatial autocorrelation analysis; the SaTScan 10.1 software was used for spatial-temporal scan statistics. Results: There were 6 715 cases of the cumulative report in Hebei Province from 2013 to 2022 without death. The annual report incidence was 0.90/100 000. The overall incidence rate showed an upward trend from 2013 to 2019, and during 2020-2021, it showed a sharp decline, but in 2022, it showed a sharp increase. Summer and autumn are the peak seasons of the epidemic. The incidence was highest in age group <1 year (48.67%), and the lowest age group in age group ≥15 years (0.45%) and mainly scattered children (78.03%); the incidence about men is higher than women. Spatial autocorrelation analysis showed that the onset of pertussis has spatial clustering, and high-high clusters were found in Langfang, Baoding, and Cangzhou, the top three countries with reported incidence. The area covered by a low-low cluster was consistent with the distribution of the corresponding low-incidence areas in this study. Space-time scan detects five statistically significant areas, and three zones were concentrated in 2022. Conclusions: The incidence of pertussis in Hebei had obvious season, population, and area-specific differences. There was obvious spatiotemporal and clustering, so the control of key areas should target the characteristics of time and space.

Roxadustat protects rat renal tubular epithelial cells from hypoxia-induced injury through the TGF-ß1/Smad3 signaling pathway.

OBJECTIVE: Roxadustat is used to treat renal anemia. The renoprotective effect of roxadustat needs to be further confirmed, and the mechanism of action is unknown. This study aims to evaluate the effect and mechanism of roxadustat in hypoxia-related nephropathy with the renal tubular epithelial cell line NRK-52E. MATERIALS AND METHODS: The cell Counting Kit-8 (CCK-8) assay was employed to assess cellular proliferation in the current investigation. Flow cytometry was used to conduct cell apoptosis analysis. The utilization of electron microscopy facilitated the identification of changes in cellular ultrastructure. Immunofluorescence was used to detect the expression trend of hypoxia-inducible factor-1α (HIF-1α). The connective tissue growth factor (CTGF), transforming growth factor-ß1 (TGF-ß1), Smad family member 3 (Smad3), p-Smad3, α-smooth muscle actin (α-SMA), collagen I, and HIF-1α were assessed by western blotting. Real-time fluorescent quantitative PCR (RT-qPCR) was used to measure TGF-ß1 and Smad3 mRNA. RESULTS: Significant growth inhibition and increased apoptosis were observed in NRK-52E cells cultured under hypoxic conditions (1% and 5% O2), which can be rescued by roxadustat. From a morphological perspective, it has been observed that roxadustat can counteract cellular damage features produced by hypoxia. These features include the contraction of the nuclear envelope and an increase in the formation of apoptotic bodies. Roxadustat increases HIF-1α expression acutely at 24 h, followed by a gradual reduction of HIF-1α expression to levels significantly below that of the hypoxia group by 72 h. Roxadustat can also inhibit hypoxia-induced increased expression of CTGF, TGF-ß1, p-Smad3, α-SMA, collagen I, and HIF-1α. Combined treatment with roxadustat and siRNA against TGF-ß1 synergistically reduced the expression of CTGF and HIF-1α, while the effect on TGF-ß1 and p-Smad3 were comparable to that of the individual treatment alone. Comparably, the combined administration of roxadustat and siRNA targeting Smad3 had a synergistic impact on diminishing the expression of CTGF. CONCLUSIONS: These findings indicate that roxadustat attenuates experimental renal fibrosis likely by inhibiting the TGF-ß1/Smad3 pathways, while its effect on CTGF and HIF-1α may involve other signaling pathways.

Estrogen as a guardian of auditory health: Tsp1-CD47 axis regulation and noise-induced hearing loss.

OBJECTIVES: This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms. METHODS: An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology. RESULTS: After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)-CD47 axis in OVX rats was discovered and verified. CONCLUSIONS: OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1-CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.

[Application of a new-type of defecator in the treatment of rectal fecal impaction].

Objective: This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction. Methods: In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications. Results: All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case. Conclusion: The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.

[Evaluation of the predictive effect of PD-L1 expression on survival in early triple-negative breast cancer].

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.

[Effects and mechanism of astragalus polysaccharide on wound healing of deep partial-thickness burns in rats].

Objective: To investigate the effects and mechanism of astragalus polysaccharide (APS) on wound healing of deep partial-thickness burns in rats. Methods: The experimental study method was used. Fifty 7-week-old male Sprague-Dawley rats were divided into normal group, simple burn group, APS group, inhibitor group, and inhibitor+APS group according to the random number table, with 10 rats in each group. Except for normal group, rats in the other 4 groups were inflicted with a deep partial-thickness burn wound on the back. Rats in normal group and simple burn group were intraperitoneally injected with normal saline, and rats in the other three groups were injected with APS and/or integrin-linked kinase (ILK) inhibitor, respectively. After 7 days of injection, the wound healing rate of rats with burns in the four groups was calculated, and the serum content of interferon-γ, interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α) in rats in 5 groups was determined by enzyme-linked immunosorbent assay (ELISA). The normal skin tissue of rats in normal group and wound tissue of rats with burns in the four groups were taken, the water content was determined and the water ratio was calculated, the content of interferon-γ, IL-2, and TNF-α was detected by ELISA, the mRNA expressions of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and ILK were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction, and the protein expressions of ILK, protein kinase B (Akt), phosphorylated Akt (p-Akt), glycogen synthetic kinase-3ß (GSK-3ß), and phosphorylated GSK-3ß (p-GSK-3ß) were detected by Western blotting. Data were statistically analyzed with one-way analysis of variance and least significant difference test. Results: After 7 days of injection, the wound healing rate of rats in APS group was (67±5)%, which was significantly higher than (52±4)% in simple burn group and (59±5)% in inhibitor+APS group (with all the P values <0.05). The wound healing rate of rats in inhibitor+APS group was significantly higher than (48±4)% in inhibitor group (P<0.05). After 7 days of injection, compared with those in serum or normal skin tissue of rats in normal group, the serum content of interferon-γ, TNF-α, IL-2 and the water ratio of wound tissue of rats in simple burn group were significantly increased (P<0.05); compared with those in APS group, the serum content of interferon-γ, TNF-α, IL-2 and the water ratio of wound tissue of rats in simple burn group and inhibitor+APS group were significantly increased (P<0.05); compared with those in inhibitor group, the serum content of interferon-γ, TNF-α, IL-2 and the water ratio of wound tissue of rats in inhibitor+APS group were significantly decreased (P<0.05). After 7 days of injection, compared with that in normal skin tissue of rats in normal group, the content of interferon-γ, TNF-α, and IL-2 in wound tissue of rats in simple burn group was significantly increased (P<0.05); compared with that in APS group, the content of interferon-γ, TNF-α, and IL-2 in wound tissue of rats in simple burn group and inhibitor+APS group was significantly increased (P<0.05); compared with that in inhibitor group, the content of interferon-γ, TNF-α, and IL-2 in wound tissue of rats in inhibitor+APS group was significantly decreased (P<0.05). After 7 days of injection, compared with those in normal skin tissue of rats in normal group, the mRNA expressions of EGF, bFGF, ILK and protein expressions of ILK, p-Akt, p-GSK-3ß in wound tissue of rats in simple burn group were significantly increased (P<0.05); compared with those in APS group, the mRNA expressions of EGF, bFGF, ILK and protein expressions of ILK, p-Akt, p-GSK-3ß in wound tissue of rats in simple burn group and inhibitor+APS group were significantly decreased (P<0.05); compared with those in inhibitor group, the mRNA expressions of EGF, bFGF, ILK and protein expressions of ILK, p-Akt, p-GSK-3ß in wound tissue of rats in inhibitor+APS group were significantly increased (P<0.05). There were no statistically significant differences in the protein expressions of Akt and GSK-3ß in normal skin tissue of rats in normal group and wound tissue of rats with burns in the four groups (P>0.05). Conclusions: APS can alleviate systemic and local inflammation, alleviate tissue edema, and promote the expressions of healing factors in rats with deep partial-thickness burns, thus to promote the wound healing, possibly by activating ILK/Akt/GSK-3ß signaling pathway.

The impact of social media on guideline-concordant cervical cancer-screening: insights from a national survey.

OBJECTIVES: Cervical cancer is one of the leading causes of cancer mortality in women, yet routine screenings lead to early detection and sometimes even prevention. Screening is an effective way to prevent cervical cancer, and it has been implemented in many countries and regions worldwide, especially in developed countries. However, the incidence of cervical cancer remains a public health problem due to screening disparities in the population. Social media engagement and overloading of online health information may be the cause of this disparity. STUDY DESIGN: Cross-sectional study. METHODS: Data from the Health Information National Trends Survey (a national survey conducted by the National Cancer Institute) was used to characterise cervical cancer screening into two dimensions; namely, high-frequency screening and guideline-concordant screening. The differences between these two screening frequency behaviours were compared by applying ordered logistic regression and binary logistic regression, and the mechanisms of guideline-concordant screening were explored. RESULTS: The factors influencing high-frequency screening and guideline-concordant screening were different. Only self-efficacy (odds ratio [OR] = 1.16; 95% confidence interval [CI] = 0.98, 1.37) had a significant positive association with the high-frequency screening behaviour. Social media engagement (OR = 0.57; 95% CI = 0.33, 0.96) was shown to have a significant negative impact on guideline-concordant screening. A theory-based mechanism of screening behaviour found that traditional health perception factors no longer influence guideline-concordant screening behaviour, whereas environmental factors (e.g., social media) significantly reduce guideline-concordant screening behaviour. CONCLUSIONS: The results from this study indicate that while the internet has become the main channel through which women acquire health resources, and social media has become a main platform for people to obtain health information, online information cannot guide people to engage in appropriate healthy behaviours. Overloading of online health information and the digital divide may lead to excessive screening. Consequently, it is important to address the screening disparity caused by health behaviours as a result of environmental factors and the digital divide.

[Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway].

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and ß-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

[Nomogram analysis of risk factors for diabetic neuropathy in primary type 2 diabetic mellitus patients in Zhejiang Province].

Objective: To investigate the risk factors of diabetic nephropathy (DN) in primary type 2 diabetes mellitus (T2DM) patients and to quantitatively analyze the risk of DN by nomogram modeling. Methods: A total of 1 588 primary T2DM patients from 17 townships and streets in Zhejiang Province were enrolled from June 2018 to August 2018 in this cross-sectional study, with an average age of (56.8±10.1) years (50.06% male) and a mean disease duration of 9 years. The clinical data, biochemical test results, and fundus photographs of all T2DM patients were collected, and logistic regression analysis was used to screen the risk factors of DN. Then, a nomogram model was used to quantitatively analyze the risk of DN. Results: DN occurred in 27.71% (440/1 588 cases) primary type 2 diabetes patients. Hemoglobin A1c (HbA1c) (OR=1.159, 95%CI 1.039-1.292), systolic blood pressure (OR=1.041, 95%CI 1.031-1.051), serum creatinine (Scr) (OR=1.011, 95%CI 1.004-1.017), serum globulin (GLOB) (OR=1.072, 95%CI 1.039-1.105), diabetic retinopathy (DR) (OR=1.463, 95%CI 1.073-1.996), education level of more than junior high school (OR=2.018, 95%CI 1.466-2.777), and moderate-intensity exercise (OR=0.751, 95%CI 0.586-0.961) were influencing factors of DN. Nomogram model analysis showed that the total score of each factor of DN ranged from 64-138 points, and the corresponding risk rate ranged from 0.1-0.9. The nomogram model also predicted a C-index value of 0.753 (95%CI 0.726-0.781) and an area under the receiver operating characteristic curve of DN of 0.753. Internal verification of the C-index reached 0.738. The model displayed medium predictive power and could be applied in clinical practice. Conclusions: HbA1c, systolic blood pressure, Scr, GLOB, DR, and more than a junior high school education are independent risk factors of DN. Nomogram modeling can more intuitively evaluate the risk of DN in primary T2DM patients.

Age-related adiposity and beta-cell function: impact on prediabetes and diabetes prevalence in middle-aged and older Han Chinese adults.

PURPOSE: To investigate the effect of aging on the prevalence of prediabetes and diabetes, and the influence of aging on the associations among adipose mass, redistribution, ß cell function, and the prevalence of hyperglycaemia. METHOD: This urban-based cross-sectional study included 1033 Chinese Han people, aged 40-65 years. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were determined by magnetic resonance imaging. The prevalence rates of prediabetes and diabetes were analyzed according to age group (40-49, 50-59, and 60-65 years). The effects of aging on abdominal fat mass, adipose distribution, insulin action indexes were also assessed. RESULTS: Prediabetes and diabetes prevalence gradually increased with age. Both SFA and VFA increased, while SFA/VFA decreased, in the 50-59 and 60-65 years age groups compared to the 40-49 years group. Homeostatic model assessment of insulin resistance (HOMA-IR) increased with fat mass. Homeostatic model assessment of beta-cell function (HOMA-ß) and early-phase insulin secretion (∆I30/∆G30) were decreased in the 60-65 years group compared to the younger age groups. Increased age, VFA, and HOMA-IR, as well as decreased HOMA-ß, were risk factors for the development of prediabetes and diabetes. The associations between central obesity and the development of prediabetes and diabetes, but not the associations of SFA/VFA, HOMA-IR, and HOMA-ß with hyperglycaemia prevalence, weakened with age. CONCLUSIONS: The prevalence of prediabetes and diabetes increased with age. Central obesity may be related stronger to the development of hyperglycaemia in younger people.

[Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation].

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

High species diversity in Diaporthe associated with citrus diseases in China.

Species in Diaporthe have broad host ranges and cosmopolitan geographic distributions, occurring as endophytes, saprobes and plant pathogens. Previous studies have indicated that many Diaporthe species are associated with Citrus. To further determine the diversity of Diaporthe species associated with citrus diseases in China, we conducted extensive surveys in major citrus-producing areas from 2017-2020. Diseased tissues were collected from leaves, fruits, twigs, branches and trunks showing a range of symptoms including melanose, dieback, gummosis, wood decay and canker. Based on phylogenetic comparisons of DNA sequences of the internal transcribed spacer regions (ITS), calmodulin (cal), histone H3 (his3), translation elongation factor 1-alpha (tef1) and beta-tubulin (tub2), 393 isolates from 10 provinces were identified as belonging to 36 species of Diaporthe, including 32 known species, namely D. apiculata, D. biconispora, D. biguttulata, D. caryae, D. citri, D. citriasiana, D. compacta, D. discoidispora, D. endophytica, D. eres, D. fusicola, D. fulvicolor, D. guangxiensis, D. hongkongensis, D. hubeiensis, D. limonicola, D. litchii, D. novem, D. passifloricola, D. penetriteum, D. pescicola, D. pometiae, D. sackstonii, D. sennicola, D. sojae, D. spinosa, D. subclavata, D. tectonae, D. tibetensis, D. unshiuensis, D. velutina and D. xishuangbanica, and four new species, namely D. gammata, D. jishouensis, D. ruiliensis and D. sexualispora. Among the 32 known species, 14 are reported for the first time on Citrus, and two are newly reported from China. Among the 36 species, D. citri was the dominant species as exemplified by its high frequency of isolation and virulence. Pathogenicity tests indicated that most Diaporthe species obtained in this study were weakly aggressive or non-pathogenic to the tested citrus varieties. Only D. citri produced the longest lesion lengths on citrus shoots and induced melanose on citrus leaves. These results further demonstrated that a rich diversity of Diaporthe species occupy Citrus, but only a few species are harmful and D. citri is the main pathogen for Citrus in China. The present study provides a basis from which targeted monitoring, prevention and control measures can be developed. Citation: Xiao XE, Liu YD, Zheng F, et al. 2023. High species diversity in Diaporthe associated with citrus diseases in China. Persoonia 51: 229-256. doi: 10.3767/persoonia.2023.51.06.

Acceleration of Brain Susceptibility-Weighted Imaging with Compressed Sensitivity Encoding: A Prospective Multicenter Study.

BACKGROUND AND PURPOSE: While three-dimensional susceptibility-weighted imaging has been widely suggested for intracranial vessel imaging, hemorrhage detection, and other neuro-diseases, its relatively long scan time has necessitated the clinical verification of recent progresses of fast imaging techniques. Our aim was to evaluate the effectiveness of brain SWI accelerated by compressed sensitivity encoding to identify the optimal acceleration factors for clinical practice. MATERIALS AND METHODS: Ninety-nine subjects, prospectively enrolled from 5 centers, underwent 8 brain SWI sequences: 5 different folds of compressed sensitivity encoding acceleration (CS2, CS4, CS6, CS8, and CS10), 2 different folds of sensitivity encoding acceleration (SF2 and SF4), and 1 without acceleration. Images were assessed quantitatively on both the SNR of the red nucleus and its contrast ratio to the CSF and, subjectively, with scoring on overall image quality; visibility of the substantia nigra-red nucleus, basilar artery, and internal cerebral vein; and diagnostic confidence of the cerebral microbleeds and other intracranial diseases. RESULTS: Compressed sensitivity encoding showed a promising ability to reduce the acquisition time (from 202 to 41 seconds) of SWI while increasing the acceleration factor from 2 to 10, though at the cost of decreasing the SNR, contrast ratio, and the scores of visual assessments. The visibility of the substantia nigra-red nucleus and internal cerebral vein became unacceptable in CS6 to CS10. The basilar artery was well-distinguished, and diseases including cerebral microbleeds, cavernous angiomas, intracranial gliomas, venous malformations, and subacute hemorrhage were well-diagnosed in all compressed sensitivity encoding sequences. CONCLUSIONS: Compressed sensitivity encoding factor 4 is recommended in routine practice. Compressed sensitivity encoding factor 10 is potentially a fast surrogate for distinguishing the basilar artery and detecting susceptibility-related abnormalities (eg, cerebral microbleeds, cavernous angiomas, gliomas, and venous malformation) at the sacrifice of visualization of the substantia nigra-red nucleus and internal cerebral vein.

[Evaluation of the efficacy and safety of combination of gemcitabine and nedaplatin for patients with HER-2 negative metastatic breast cancer].

Objective: To assess the therapeutic efficacy and safety of the gemcitabine combined with nedaplatin (GN) chemotherapy for metastatic human epidermal growth factor receptor-2 (HER-2) negative breast cancer patients. Methods: Forty-five patients with HER-2 negative recurrent metastatic breast cancer who had received prior adjuvant or neoadjuvant therapy with anthracycline and/or taxanes were enrolled. All the patients received GN regime from January 2014 to February 2019. The therapeutic efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST) 1.1. The adverse response was evaluated and monitored according to common terminology criteria for adverse events (CTCAE). The progression-free survival (PFS) and overall survival (OS) and prognostic factors were also analyzed. Results: All of the 45 patients received 4 course GN, 1 of them achieved complete response, 21 achieved partial response. The objective response rate was 48.9 (95% CI: 33.7%-64.1%). Grade 3-4 hematological toxicities include leukopenia occurred in 10 (22.2%) of patients, neutropenia in 13 (28.9%) patients, and thrombocytopenia in 8 (17.6%) patients. The grade 3-4 hematological toxicities mainly manifested as nausea and vomiting, and the incidence was 4.4% (2/45). Among the 45 patients, 34 died, the median PFS was 5.1 (95% CI: 3.9-6.1) months and the median OS was 17.6 (95% CI: 13.1-20.9) months. Conclusion: The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for metastatic breast cancer patients previously treated with anthracyclines and/or taxanes.

[Interpretation of "View of Xing & Shen" of TCM by four scholastic sects of Jin-Yuan dynasties and its background].

The concept of "Xing & Shen"(Body and spirit) and their relationship are important philosophical categories and basic issues in life cognition. The view of "body and spirit" in Chinese medicine is the inheritance and development of the concept of "form and spirit" in ancient Chinese philosophy; the view of body-spirit syncretism is one of the elements of the original thinking mode in traditional Chinese medicine, which reflects the holism of TCM. This article selects interpretations of "body and spirit" form the works of the four great physicians of the Jin and Yuan period as the starting point to find out the internal connection between their academic innovation and their identities of Confucian physician, as well as their classic study, based on the social background of the Jin and Yuan Period.

Modular gene analysis reveals distinct molecular signatures for subsets of patients with cutaneous lupus erythematosus.

BACKGROUND: Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease with clinical sequelae such as itching, dyspigmentation and scarring. OBJECTIVES: We applied a previously described modular analysis approach to assess the molecular heterogeneity of patients with CLE. METHODS: Whole-blood transcriptomes of RNA sequencing data from a racially and ethnically diverse group of patients with CLE (n = 62) were used to calculate gene co-expression module scores. An unsupervised cluster analysis and k-means clustering based on these module scores were then performed. We used Fisher's exact tests and Kruskal-Wallis tests to compare characteristics between patient clusters. RESULTS: Six unique clusters of patients with CLE were identified from the cluster analysis. We observed that seven inflammation modules were elevated in two clusters of patients with CLE. Additionally, these clusters were characterized by interferon, neutrophil and cell-death signatures, suggesting that interferon-related proteins, neutrophils and cell-death processes could be driving the inflammatory response in these subgroups. Three different clusters had a predominant T-cell signature, which were supported by lymphocyte counts. CONCLUSIONS: Our data support a diverse molecular profile in CLE that further adds to the clinical variations of this skin disease, and may affect disease course and treatment selection. Future studies with a larger and diverse cohort of patients with CLE are warranted to confirm these findings.