CXCR4/CXCL12 mediate autocrine cell- cycle progression in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise in connective tissue surrounding peripheral nerves. They occur sporadically in a subset of patients with neurofibromatosis type 1 (NF1). MPNSTs are highly aggressive, therapeutically resistant, and typically fatal. Using comparative transcriptome analysis, we identified CXCR4, a G-protein-coupled receptor, as highly expressed in mouse models of NF1-deficient MPNSTs, but not in nontransformed precursor cells. The chemokine receptor CXCR4 and its ligand, CXCL12, promote MPNST growth by stimulating cyclin D1 expression and cell-cycle progression through PI3-kinase (PI3K) and ß-catenin signaling. Suppression of CXCR4 activity either by shRNA or pharmacological inhibition decreases MPNST cell growth in culture and inhibits tumorigenesis in allografts and in spontaneous genetic mouse models of MPNST. We further demonstrate conservation of these activated molecular pathways in human MPNSTs. Our findings indicate a role for CXCR4 in NF1-associated MPNST development and identify a therapeutic target.

A Non-canonical PDK1-RSK Signal Diminishes Pro-caspase-8-Mediated Necroptosis Blockade.

Necroptosis induction in vitro often requires caspase-8 (Casp8) inhibition by zVAD because pro-Casp8 cleaves RIP1 to disintegrate the necrosome. It has been unclear how the Casp8 blockade of necroptosis is eliminated naturally. Here, we show that pro-Casp8 within the necrosome can be inactivated by phosphorylation at Thr265 (pC8T265). pC8T265 occurs in vitro in various necroptotic cells and in the cecum of TNF-treated mice. p90 RSK is the kinase of pro-Casp8. It is activated by a mechanism that does not need ERK but PDK1, which is recruited to the RIP1-RIP3-MLKL-containing necrosome. Phosphorylation of pro-Casp8 at Thr265 can substitute for zVAD to permit necroptosis in vitro. pC8T265 mimic T265E knockin mice are embryonic lethal due to unconstrained necroptosis, and the pharmaceutical inhibition of RSK-mediated pC8T265 diminishes TNF-induced cecum damage and lethality in mice by halting necroptosis. Thus, phosphorylation of pro-Casp8 at Thr265 by RSK is an intrinsic mechanism for passing the Casp8 checkpoint of necroptosis.

Gut stem cell necroptosis by genome instability triggers bowel inflammation.

The aetiology of inflammatory bowel disease (IBD) is a multifactorial interplay between heredity and environment1,2. Here we report that deficiency in SETDB1, a histone methyltransferase that mediates the trimethylation of histone H3 at lysine 9, participates in the pathogenesis of IBD. We found that levels of SETDB1 are decreased in patients with IBD, and that mice with reduced SETDB1 in intestinal stem cells developed spontaneous terminal ileitis and colitis. SETDB1 safeguards genome stability3, and the loss of SETDB1 in intestinal stem cells released repression of endogenous retroviruses (retrovirus-like elements with long repeats that, in humans, comprise approximately 8% of the genome). Excessive viral mimicry generated by motivated endogenous retroviruses triggered Z-DNA-binding protein 1 (ZBP1)-dependent necroptosis, which irreversibly disrupted homeostasis of the epithelial barrier and promoted bowel inflammation. Genome instability, reactive endogenous retroviruses, upregulation of ZBP1 and necroptosis were all seen in patients with IBD. Pharmaceutical inhibition of RIP3 showed a curative effect in SETDB1-deficient mice, which suggests that targeting necroptosis of intestinal stem cells may represent an approach for the treatment of severe IBD.

A dual functional tunable terahertz metamaterial absorber based on vanadium dioxide.

A dual-functional switchable metamaterial absorber (MMA) based on vanadium dioxide (VO2), which achieves flexible switching between broadband absorption and four-band absorption by adjusting the VO2 conductivity, was proposed. The device has a broadband absorption function when VO2 is in the metal phase, and the conductivity is 3 × 105 S m-1. Numerical simulation shows that the absorption rate of the device reaches over 90% in the frequency range of 3.36-6.98 THz. The absorber exhibits polarization insensitivity and wide-angle absorption to transverse electric (TE) and transverse magnetic (TM) waves. When VO2 is in the insulator phase, and the conductivity is 3 × 102 S m-1, the device switches to a narrowband absorber with a band-efficient absorption function. Numerical simulation shows that the device has an absorption rate of 99.7% at 2.39 THz, 98.3% at 2.83 THz, 95.6% at 3.84 THz, and 96.1% at 4.61 THz. It can be used as a sensor with high sensitivity. In addition, to verify the absorption mechanism of the absorber, we introduced impedance matching theory to analyze the device. Finally, the influence of structural parameters on the performance of resonators was investigated. Through the joint action of multi-layer structures, the proposed MMA concentrates broadband and narrowband absorption functions on one device, achieving flexible switching between tasks without changing the structure. The switchable metamaterial absorber designed through simple tuning methods has broad application prospects in stealth technology and thermal emitters. It provides a wide range of ideas for the design of terahertz functional devices.

Supraglottic Jet Oxygenation and Ventilation to Minimize Hypoxia in Patients Receiving Flexible Bronchoscopy Under Deep Sedation: A 3-Arm Randomized Controlled Trial.

BACKGROUND: Hypoxia often occurs due to shared airway and anesthetic sedation-induced hypoventilation in patients receiving flexible bronchoscopy (FB) under deep sedation. Previous evidence has shown that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) reduces the incidence of hypoxia during FB. This study aimed to investigate the extent to which SJOV via WNJ could decrease the incidence of hypoxia in patients under deep sedation as compared to oxygen supplementation via WNJ alone or nasal catheter (NC) for oxygen supplementation during FB. METHODS: This was a single-center 3-arm randomized controlled trial (RCT). Adult patients scheduled to undergo FB were randomly assigned to 3 groups: NC (oxygen supplementation via NC), low-pressure low-flow (LPLF) (low-pressure oxygen supplementation via WNJ alone), or SJOV (high-pressure oxygen supplementation via WNJ). The primary outcome was hypoxia (defined as peripheral saturation of oxygen [Sp o2 ] <90% lasting more than 5 seconds) during FB. Secondary outcomes included subclinical respiratory depression or severe hypoxia, and rescue interventions specifically performed for hypoxia treatment. Other evaluated outcomes were sore throat, xerostomia, nasal bleeding, and SJOV-related barotraumatic events. RESULTS: One hundred and thirty-two randomized patients were included in 3 interventions (n = 44 in each), and all were included in the final analysis under intention to treat. Hypoxia occurred in 4 of 44 patients (9.1%) allocated to SJOV, compared to 38 of 44 patients (86%) allocated to NC, with a relative risk (RR) for hypoxia, 0.11; 98% confidence interval (CI), 0.02-0.51; P < .001; or to 27 of 44 patients (61%) allocated to LPLF, with RR for hypoxia, 0.15; 95% CI, 0.04-0.61; P < .001, respectively. The percentage of subclinical respiratory depression was also significantly diminished in patients with SJOV (39%) compared with patients with NC (100%) or patients with LPLF (96%), both P < .001. In SJOV, no severe hypoxia event occurred. More remedial interventions for hypoxia were needed in the patients with NC. Higher risk of xerostomia was observed in patients with SJOV. No severe adverse event was observed throughout the study. CONCLUSIONS: SJOV via WNJ effectively reduces the incidence of hypoxia during FB under deep sedation.

Focal length switchable metalens based on vanadium dioxide.

A metalens is a flat lens that can control the phase of light so that dispersed light can be reconcentrated. This study devised a tunable metalens with a switchable focal length based on the phase transition properties of vanadium dioxide (V O 2). The unit structure comprises three layers from bottom to top: gold, polyimide, and two square resonant rings. The metalens can not only transform incident x-polarized waves into y-polarized waves but also achieve beam focusing simultaneously. The designed metalens achieves polarization conversion efficiency at an operating frequency of 0.8 THz. In the insulating state of V O 2, the beam focal point is at L=1914µm; in the metallic state, the wave converges at L=982µm, closely aligning with the predetermined focal length. By controlling external temperature, focal point switching can be achieved, making it highly versatile in practical applications.

Congenital trans-sellar trans-sphenoidal encephalocele: a systematic review of diagnosis, treatment, and prognosis.

PURPOSE: Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is the primary treatment, transitioning from frontal craniotomy to endoscopic methods, offering improved outcomes. Yet, more studies are needed. A comprehensive review on trans-sellar trans-sphenoidal encephalocele (TSTSE) is missing. Our study aims to fill this gap, offering a comprehensive perspective for physicians. METHODS: This review adhered to the PRISMA guideline. Eligible studies focused on human subjects, specifically trans-sellar encephaloceles, and provided comprehensive treatment details. English language articles published up to April 11th, 2023, were considered. Two trained researchers conducted article screening using consistent criteria. Data extraction covered various aspects, including clinical presentation, surgical methods, and outcomes, with results presented descriptively in two tables. Due to the rarity of this congenital anomaly, meta-analysis and publication bias assessment were not feasible. Data extraction was independently conducted by two reviewers, with subsequent cross-verification. RESULTS: A total of 36 patients were identified from 14 studies, the most frequently observed clinical presentation was dyspnea (41.67%) and the most frequently observed accompanying anomaly was cleft lip/palate (55.56%). CT and MRI were adopted in nearly all the cases, and trans-nasal approach was the most often used surgical approach (57.14%) with the 'soft material combination' the most commonly used method for cranial base repairment (35.71%). A total of two deaths occurred and diabetes insipidus was the most common perioperative complication which occurred in six surgery patients (21.43%). CONCLUSION: TSTSE predominantly affects males and presents with dyspnea, visual deficits, pituitary insufficiency, and cranial base-related symptoms. Early diagnosis is critical, with advanced imaging playing a key role. Endocrine assessment is vital for hormone management. Surgery offers symptom relief but entails risks, including reported fatalities and complications. The choice between surgery and conservative management requires careful deliberation. The trans-nasal approach is favored for its reduced trauma, yet further research is necessary to validate this preference.

Pentacyclic triterpene-amino acid derivatives induced apoptosis and autophagy in tumor cells, affected the JNK and PI3K/AKT/mTOR pathway.

A series of pentacyclic triterpene-amino acid derivatives were synthesized and tested for anti-proliferative activity. The results showed that most of the target compounds had good anti-proliferative activity. 2c did not contain protecting groups and hydrochloride, had excellent cytotoxicity, so it had been selected for further study in the mechanism of action in T24 cells. The data from transcriptome sequencing indicated that 2c was found to be closely related to apoptosis and autophagy. Observation of fluorescence staining and analysis from flow cytometry demonstrated that 2c induced apoptosis and cause cell cycle arrest in S/G2 phase in T24 cells. Molecular mechanism studies exhibited that 2c induced apoptosis in the intrinsic and extrinsic pathways. 2c also induced cellular autophagy in T24 cells. Results from Western Blotting showed that 2c could activate JNK pathway and inhibit PI3K/AKT/mTOR pathway. In conclusion, 2c was deserved further investigation in the field of anti-tumor.

Risk Factors for Postoperative Puncture Site Bleeding after Interventional Treatment of Cerebrovascular Disease via Common Femoral Artery Puncture: A Retrospective Analysis of 710 Cases.

This study aimed to identify the risk factors associated with puncture site bleeding following percutaneous puncture of the common femoral artery during interventional treatment of cerebrovascular disease (CVD). A retrospective analysis was conducted on 710 patients who underwent interventional treatment for CVD via femoral artery puncture. Among them, 26 individuals (3.66%) experienced bleeding at the femoral artery puncture site. Binary logistic regression analysis was performed to identify risk factors for puncture site bleeding. The impact of salt bag compression on postoperative bleeding was evaluated in patients with intermediate to high bleeding risk scores. The bleeding group showed higher blood pressure, lower platelet counts, longer prothrombin time and activated partial thromboplastin time, as well as a higher prevalence of larger vascular sheath sizes and variations in the timing of anti-coagulant and anti-platelet therapy administration. The bleeding risk score was higher in the bleeding group, indicating its predictive value for bleeding risk. Higher bleeding risk score, unstable blood pressure, repeated puncture, and serious vascular conditions were significant risk factors for puncture site bleeding. Application of salt bag compression for a duration of 2 hours reduced postoperative puncture site bleeding in patients with intermediate to high bleeding risk scores. Our study identified several significant risk factors for puncture site bleeding after cerebral vascular intervention via femoral artery puncture, including the bleeding risk score, blood pressure, repeated puncture, and vascular conditions. Implementing salt bag compression as a preventive measure can help mitigate bleeding complications in these high-risk patients.

Evaluation of career planning group counseling and its effectiveness for intern male nursing students.

OBJECTIVE: To investigate the influence of group counselling on the career planning and career maturity of male nursing students. METHOD: Sixty male nursing students were randomly selected from a specific-level first-class hospital in Hunan Province from July to August 2020 by using the convenience sampling method and were subsequently divided into the control group and the experimental group using the random number table method. The control group received routine pre-job training, including aspects concerning the hospital profile, nurse etiquette, nursing core systems, professional ethics, nursing emergency treatment and career prospects and planning. In the experimental group, career planning group counselling was added after the regular pre-service training (once a week) with each session lasting 2 h for a total of six training sessions. At six weeks and three months after the intervention, the career status evaluation scale and the college students' career maturity scale were used to compare the career planning and career maturity status of the two groups of male nursing students. RESULTS: After six weeks and three months of intervention, all the dimensions and total scores of both the career status evaluation scale and the career maturity scale in the experimental group were superior to those in the control group with statistically significant differences (all P < 0.05). The repeated measures of variance analysis indicated that the differences in the total score for career planning and the four dimensions in terms of intergroup effect, time effect and interaction effect between the two groups were statistically significant (P < 0.05). The intergroup effect, time effect and interaction effect of the total score for vocational maturity, career goal, career confidence, career value, career freedom and career reference of the two groups were statistically significant (P < 0.05), while the time effect of the relative dependency dimension was also statistically significant (P < 0.05). CONCLUSION: Group counselling can significantly improve the career planning and career maturity status of male nursing students and has a certain long-term effect.

Shielded geomagnetic field accelerates glucose consumption in human neuroblastoma cells by promoting anaerobic glycolysis.

A shielded geomagnetic field, also called the hypomagnetic field (HMF), interferes with the metabolic processes of various cells and animals exhibiting diverse effects in different models, however, its underlying mechanism remains largely unknown. In this study, we assessed the effect on the energy metabolism of SH-SY5Y cells in HMF and found that HMF-induced cell proliferation depends on glucose supply. HMF promoted SH-SY5Y cell proliferation by increasing glucose consumption rate via up-regulating anaerobic glycolysis in the cells. Increased activity of LDH, a key member of glycolysis, was possibly a direct response to HMF-induced cell proliferation. Thus, we unveiled a novel subcellular mechanism underlying the HMF-induced cellular response: the up-regulation of anaerobic glycolysis and repression of oxidative stress shifted cellular metabolism more towards the Warburg effect commonly observed in cancer metabolism. We suggest that cellular metabolic profiles of various cell types may determine HMF-induced cellular effects, and a magnetic field can be applied as a non-invasive regulator of cell metabolism.

A new potential risk: The impacts of Klebsiella pneumoniae infection on the histopathology, transcriptome and metagenome of Chinese mitten crab (Eriocheir sinensis).

Klebsiella pneumoniae is a common conditional pathogen found in natural soil water sources and vegetation and can infect invertebrates, vertebrates, and plants. In this study, we isolated K. pneumoniae from the hepatopancreas of the Chinese mitten crab (Eriocheir sinensis) for the first time and then we analysed its effects of on the histopathological changes, the transcriptome of the hepatopancreas, and the gut microbiota of this crab species. The findings of this study showed that K. pneumoniae infection has led to significant structural changes in the hepatopancreas, such as the production of vacuolated tissue structures, disorganized cell arrangement, and lysis of some hepatopancreatic cells. Also, the infection caused activation of the antioxidant-related enzymes such as SOD and CAT by inducing oxidative stress. The transcriptome of the hepatopancreas identified 10,940 differentially expressed genes (DEGs) in the susceptible (SG) groups and control (CG) groups, and 8495 DEGs in the SG groups and anti-infective (AI) groups. The KEGG pathway revealed upregulated DEGs caused by K. pneumoniae infection that involved in the immune response and apoptotic functional pathways, and also downregulated DEGs involved in the digestive absorption, metabolic, and biosynthetic signaling pathways. Meanwhile, metagenics sequencing revealed that at the phylum, class, order, family, and genus levels, K. pneumoniae infection altered the composition of the gut microbiota of E. sinensis, through increasing the abundance of Prolixibacteraceae, Enterobacterales, and Roseimarinus and decreasing the abundance of Alphaproteobacteria. The flora structure has also been changed between the SG and AI groups, with the abundance of Firmicutes, Erysipelotrichales, and Erysipelotrichaceae that were significantly decreased in the SG groups than in the AI groups. But, the abundance of Acinetobacter was considerably higher than in the AI group. In summary, K. pneumoniae infection induced oxidative stress in E. sinensis, triggered changes in immune-related gene expression, and caused structural changes in the gut microbiota. This study provides data to support the analysis of bacterial infection probes in several crustacean species.

A pilot study of combined optical coherence tomography and diffusion tensor imaging method for evaluating microstructural change in the visual pathway of pituitary adenoma patients.

BACKGROUND: RNFL thickness measured by optical coherence tomography (OCT) and visual pathway measured by diffusion tensor imaging (DTI) can be used to predict visual field recovery, respectively. However, the relationship between RNFL thickness and visual pathway injury in patients with pituitary adenoma (PA) remains unclear. This study aims to evaluate the combining DTI and OCT methods in observing the microstructural change in the visual pathway in patients with PA. METHODS: Twenty-nine patients who were diagnosed with PA were included in the study group, and 29 healthy subjects were included as the control group. OCT detected the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) and ganglion cell layer (GCL). DTI measured the values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Correlation between CP-RNFL and GCL thickness and FA and ADC values was analyzed in the study group. RESULTS: Compared with the control group, the FA values of the bilateral optic nerve, chiasma, bilateral optic tract, and left optic radiation in the study group were reduced, and the ADC values of the bilateral optic nerve and optic chiasma were increased. Correlation analysis showed that the FA value of the optic chiasma was positively correlated with the average thickness of RNFL, the CP-RNFL thickness in the nasal and temporal retinal quadrants in both eyes, as well as the thickness of macular ring GCL in the nasal, supra, and inferior quadrants. The FA values of the optic nerve, optic chiasma, optic tract, and optic radiation were positively correlated with CP-RNFL thickness in the nasal and temporal quadrants. CONCLUSION: Combined DTI and OCT can provide a comprehensive understanding of the microscopic changes in the structure and function of the whole visual pathway in patients with PA.

Leaf spot on Photinia × fraseri caused by Neopestalotiopsis asiatica in China.

Photinia × fraseri is a well-known evergreeen ornamental tree. Owing to its flower-like red leaves and its ability to tolerate stressful environments, P. fraseri is widely cultured as a fast-growing hedge in southern China. From July to September in 2021, a disease with symptoms similar to leaf spot was extensively observed on P. fraseri in Daozhen county (28° 51 'N, 107° 57 'E), Zunyi, Guizhou province, China. About 500 plants were surveyed and the incidence of leaf spot on P. fraseri leaves was 35% to 70%, significantly reducing the ornamental and economic value. The symptomatic leaves displayed irregular, watery dark brown lesions with black conidiomata in gray centers, and 10 symptomatic leaves were collected from 10 trees. After surface sterilization (0.5 min in 75% ethanol and 2 min in 3% NaOCl, washed three times with sterilized distilled water) (Fang 2007), small pieces of symptomatic leaf tissue (0.2 × 0.2 cm) were plated on potato dextrose agar (PDA) and incubated at 25°C for about 7 days. Three single-spore isolates, GZAAS 21-0327, GZAAS 21-0328 and GZAAS 21-0329, were obtained, which were identical in morphology and molecular analysis. Therefore, the representative isolate GZAAS 21-0328 was used for further study. The pathogenicity of GZAAS 21-0328 was tested through a pot assay. Ten healthy plants were scratched with a sterilized needle on the leaves. Plants were inoculated by spraying a spore suspension (106 spores mL-1) of GZAAS 21-0328 onto leaves until runoff, and the control leaves sprayed with sterile water. The plants were maintained at 28°C with high relative humidity (95%) in a growth chamber. The pathogenicity test was carried out three times (Fang 2007). The symptoms developed on all inoculated leaves but not on the control leaves. The lesions were first visible 72 h after inoculation, and typical lesions similar to those observed on field plants appeared after 15 days. The same fungus was reisolated and identified based on the morphological characterization and molecular analyses (ITS, TUB and TEF) from the infected leaves but not from the noninoculated leaves. Results of pathogenicity experiments of isolated fungi fulfilled Koch's postulates. Fungal colonies on PDA were villiform, creamy-white and sparse aerial mycelium on the surface with black, gregarious conidiomata. The conidia were fusoid, ellipsoid, straight to slightly curved, 4-septate, septa darker than the rest of the cell, and 23.0 (21.0 to 27.0) × 6.0 (5.0 to 7.0) µm (n=50). The morphological features were consistent with the descriptions of Neopestalotiopsis asiatica Maharachch. & K.D. Hyde (Maharachchikumbura et al. 2012; Maharachchikumbura et al. 2014; Farr et al. 2022). The pathogen was confirmed to be N. asiatica by amplification and sequencing of the internal transcribed spacer region (ITS), the partial ß-tubulin (TUB) and partial translation elongation factor 1-alpha (TEF) genes using primers ITS4/ITS5, T1/Bt-2b and EF1-728F/EF-2, respectively (Maharachchikumbura et al. 2014). The sequences of PCR products were deposited in GenBank with accession numbers OK563071 (ITS), OK584020 (TUB) and OK663023 (TEF). BLAST searches of the obtained sequences revealed 100% (482/482 nucleotides), 99.05% (419/421 nucleotides), and 99.33% (891/897 nucleotides) homology with those of N. asiatica in GenBank (JX398983, JX399018 and JX399049, respectively). Phylogenetic analysis (MEGA 6.0) using the maximum likelihood method placed the isolate GZAAS 21-0328 in a well-supported cluster with N. asiatica. The pathogen was thus identified as N. asiatica based on the morphological characterization and molecular analyses. To our knowledge, this is the first report of leaf spot on P. fraseri caused by N. asiatica in China. This study provides valuable information for the identification and control of the leaf spot on Photinia × fraseri.

First Report of Colletotrichum fioriniae Causing Anthracnose on Rhododendron delavayi in China.

Rhododendron delavayi Franch, a member of Ericaceae family, is globally famous for its garden flowers with significant ornamental value (Liu et al., 2020). In July 2020 and 2021, a disease survey of R. delavayi groves was conducted in Baili Azalea Forest Area (N27°10'-27°20', E 105°04'-106°04'). We arbitrarily selected an area with around 280 R. delavayi trees covering 2.5 hectares in R. delavayi grove where 20-35% of leaves showed symptoms of anthracnose. Typical symptoms included elliptical to irregularly shaped brown lesions on leaves and masses of black dots clustered on it. About 30 pieces of leaves with anthracnose lesions were collected. A few black dots were picked from the lesions with a sterilized needle, plated on water agar and incubated at 25℃ for 12 h to observe spore germination (Fang, 2007). Then the germinated spores were transferred onto PDA medium for further purification and morphological observation. Fourteen single-spore isolates with similar morphology were obtained. The surface of the colony was white or gray and spongy; the edge was smooth; and the back side was pinkish brown after 7 days of growth on PDA. Conidia were spindle-shaped, transparent, 11.1-16.6×3.6-4.9 µm (n=50). Appressorium from conidia was nearly ovate or proximate, brown or dark brown in color, 4.3-10.3 ×3.2-7.6 µm (n=50). These characteristics are consistent with Colletotrichum fioriniae reported by Shivas and Tan (2009). DNA was extracted from a representative isolate MYDJ12. The internal transcribed spacer region (ITS), the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ß-tubulin (TUB), actin (ACT), and chitin synthase 1 (CHS-1) genes were amplified using primer pairs described by Damm et al. (2012). The sequences were deposited in GenBank with accession number MW692854 (ITS), MW727518 (GAPDH), MW727519 (TUB2), MW727520 (ACT), and MW727521 (CHS-1). BLASTN searches of the ITS, GADPH, TUB2, ACT and CHS-1 genes revealed 100% (540/540 nucleotides), 100% (254/254 nucleotides), 99.38% (4488/491 nucleotides), 98.77% (242/245 nucleotides) and 100% (282/282 nucleotides) homology with those of C. fioriniae CBS:128517T in GenBank (NR_111747, JQ948622, JQ949943, JQ949613 and JQ948953 respectively). The phylogenetic tree showed the isolate MYDJ12 to cluster with C. fioriniae CBS:128517T. Finally, two-year old R. delavayi plants (n=5) were inoculated by wounding with a syringe needle and placing 10 µL of spore suspension (106 spores per mL) of the isolate MYDJ12 on three leaves per plant. Control leaves were inoculated with sterile water. The experiment was conducted twice. Inoculated leaves were wrapped in parafilm tape and then the plants were placed in a greenhouse at 25°C with high relative humidity (90 to 95%). Seven days after incubation, brown lesions appeared, similar to those observed in the grove. Black dots clustered on the lesions after 15 days. Re-isolation was conducted 20 days after inoculation. From all the five inoculated plants, similar symptoms were observed, and the same pathogen was re-isolated. One of the isolates was selected for morphological observation and multi-gene (ITS, GAPDH, ACT, TUB2 and CHS-1) analysis indicated the reisolated fungus to be C. fioriniae. No fungal pathogens were isolated from mock inoculated plants. This study can provide effective management and useful information for the control of this disease on R. delavayi in Baili Azalea Forest Area. References: Damm, U., et al. 2012. Stud Mycol 73: 37. Fang, Z. D. 2007. Research Methods of Plant Diseases (Third edition). China Agriculture Press. Liu, J., et al. 2020. Mitochondrial DNA B 5:37. Shivas, R, G; Tan, Y, P. 2009. Fungal Divers 39:111.

NF1 regulation of RAS/ERK signaling is required for appropriate granule neuron progenitor expansion and migration in cerebellar development.

Cerebellar development is regulated by a coordinated spatiotemporal interplay between granule neuron progenitors (GNPs), Purkinje neurons, and glia. Abnormal development can trigger motor deficits, and more recent data indicate important roles in aspects of memory, behavior, and autism spectrum disorders (ASDs). Germline mutation in the NF1 tumor suppressor gene underlies Neurofibromatosis type 1, a complex disease that enhances susceptibility to certain cancers and neurological disorders, including intellectual deficits and ASD. The NF1 gene encodes for neurofibromin, a RAS GTPase-activating protein, and thus negatively regulates the RAS signaling pathway. Here, using mouse models to direct conditional NF1 ablation in either embryonic cerebellar progenitors or neonatal GNPs, we show that neurofibromin is required for appropriate development of cerebellar folia layering and structure. Remarkably, neonatal administration of inhibitors of the ERK pathway reversed the morphological defects. Thus, our findings establish a critical cell-autonomous role for the NF1-RAS-ERK pathway in the appropriate regulation of cerebellar development and provide a basis for using neonatal ERK inhibitor-based therapies to treat NF1-induced cerebellar disorders.

Individual Identification in Facial Appearance Biometrics Based on Macroscopical Comparison.

Individual identification is one of the research hotspots in the practice of forensic science, and the judgment is usually built on the comparison of the unique biological characteristics of the individual, such as fingerprints, iris and DNA. With the dramatic increase in the number of cases related to video image investigations, there is an increasing need for the technology to identify individuals based on the macroscopic comparison of facial appearance biometrics. At present, with the introduction of computer three-dimensional (3D) modeling and 3D superimposition comparison technology, considerable progress has been made in individual identification methods based on macroscopic comparison of facial appearance biometrics. This paper reviews individual facial appearance biometric methods based on macroscopical comparison, comprehensively analyzes the advantages and limitations of different methods, and puts forward recommendations and prospects for subsequent research.

Dual-function chimeric antigen receptor T cells targeting c-Met and PD-1 exhibit potent anti-tumor efficacy in solid tumors.

Purpose Programmed cell death 1 (PD-1), which is upregulated under the continuous induction of the tumor microenvironment, causes chimeric antigen receptor (CAR)-T cell hypofunction via interaction with programmed death ligand 1 (PD-L1). This study aimed to construct CAR-T cells that are resistant to PD-1 inhibition to improve the effect of CAR-T cells in solid tumors. Methods We constructed a type of dual-function CAR-T cell that targets tumor-associated antigen c-Met and blocks the binding of PD-1 with PD-L1. The expression of c-Met, PD-L1, and inhibitory receptors was measured using flow cytometry. The cytotoxicity, cytokine release, and differentiation level of CAR-T cells were determined using lactate dehydrogenase release assay, enzyme-linked immunosorbent assay, and flow cytometry, respectively. The levels of p-Akt, p-MAPK, caspase-3, and Bcl2 were detected by western blot. The in vivo anti-tumor effect was evaluated using tumor xenograft models. Results Dual-function CAR-T cells could mediate enhanced active signals upon encountering target antigens and had targeted cytotoxicity to target cells. However, the cytotoxicity of c-Met-CAR-PD-1+ T cells was impaired due to the interaction of PD-1 with PD-L1. By blocking the binding of PD-1 and PD-L1, the novel dual-function CAR-PD-1+ T cells could maintain cytotoxicity to PD-L1+ tumor cells. In tumor tissue, the dual-function CAR-T cells showed lower inhibitory receptor expression and lower differentiation characteristics, which resulted in potent anti-tumor effects and prolonged survival in PD-L1+ tumor xenograft models compared to single-target CAR-T cells. Conclusion These results confirm that the novel dual-function CAR-T cells exhibit stronger anti-tumor activity against solid tumors than traditional single-target CAR-T cells and present a new approach that enhance the activity of CAR-T cells in solid tumors.

Expression of Cell Division Cycle Protein 45 in Tissue Microarrays and the CDC45 Gene by Bioinformatics Analysis in Human Hepatocellular Carcinoma and Patient Outcomes.

BACKGROUND Hepatocellular carcinoma (HCC) causes a heavy disease burden worldwide. Cell division cycle 45 (Cdc45) and its encoding gene (CDC45) have been studied for a long time, but their expression patterns and roles in liver carcinogenesis and advanced HCC deterioration are still incompletely understood. This study integrated tissue microarray and bioinformatics analyses to explore the expression and clinical value of CDC45 and Cdc45 in HCC. MATERIAL AND METHODS In HCC, the expression and relationships with clinic-pathological parameters of CDC45 and Cdc45 were investigated by integrating the RNA-sequencing data, downloaded from The Cancer Genome Atlas and Oncomine databases, and tissue microarray with immunohistochemistry staining. Co-expressed genes and genetic alterations of CDC45 separately obtained from Oncomine and cBioPortal databases were identified to shed light on the potential mechanisms of CDC45 in HCC. RESULTS CDC45 and Cdc45 were both overexpressed in HCC tissues, and the CDC45 level progressively increased from stage I to III. The survival outcomes of the group with high CDC45 expression were significantly worse compared with the group with low expression. Amplification and deep deletion were 2 major significant alteration types in HCC patients, and the outcomes were worse in patients with altered versus unaltered CDC45. NUDT1, E2F1, CCNE2, MCM5, and CENPM were identified as the most significantly co-expressed genes. CONCLUSIONS CDC45 and Cdc45 were both upregulated in HCC, and increased expression levels and genetic alternations of CDC45 were correlated with worse prognosis in HCC patients. CDC45 may promote HCC by co-expressing with NUDT1, E2F1, CCNE2, MCM5, and CENPM.

First Report of Colletotrichum boninense Causing Anthracnose on Rosa chinensis in China.

Chinese rose (Rosa chinensis Jacq.) is cultivated for edible flowers in southwestern China (Zhang et al. 2014). In March 2020, a leaf spot disease was observed on about 3-5% leaves of Chinese rose cultivar 'Mohong' in Guizhou Botanical Garden (26°37' 45'' N, 106°43' 10'' E), Guiyang, Guizhou province, China. The symptomatic plants displayed circular, dark brown lesions with black conidiomata in grey centers on leaves, and leaf samples were collected. After surface sterilization (0.5 min in 75% ethanol and 2 min in 3% NaOCl, washed 3 times with sterilized distilled water) (Fang 2007), small pieces of symptomatic leaf tissue (0.3 × 0.3 cm) were plated on potato dextrose agar (PDA) and incubated at 28oC for about 7 days. Two single-spore isolates, GZUMH01 and GZUMH02, were obtained, which were identical in morphology and molecular analysis. Therefore, the representative isolate GZUMH01 was used for further study. The pathogenicity of GZUMH01 was tested through a pot assay. Ten healthy plants were scratched with a sterilized needle on the leaves. Plants were inoculated by spraying a spore suspension (106 spores ml-1) onto leaves until runoff, and the control leaves sprayed with sterile water. The plants were maintained at 25°C with high relative humidity (90 to 95%) in a growth chamber. The pathogenicity test was carried out three times using the method described in Fang (2007). The symptoms developed on all inoculated leaves but not on the control leaves. The lesions were first visible 48 h after inoculation, and typical lesions similar to those observed on field plants after 7 days. The same fungus was re-isolated from the infected leaves but not from the non-inoculated leaves, fulfilling Koch's postulates. Fungal colonies on PDA were villiform and greyish. The conidia were abundant, oval-ellipsoid, aseptate, 15.8 (13.7 to 18.8) × 5.7 (4.3 to 6.8) µm. The fungal colonies, hyphae, and conidia were consistent with the descriptions of Colletotrichum boninense Moriwaki, Toy. Sato & Tsukib. (Damm et al. 2012; Moriwaki et al. 2003). The pathogen was confirmed to be C. boninense by amplification and sequencing of the internal transcribed spacer region (ITS), the glyceraldehyde-3-phosphate dehydrogenase (GADPH), actin (ACT), and chitin synthase 1 (CHS-1) genes using primers ITS1/ITS4, GDF1/GDR1, ACT512F/ACT783R, and CHS-79F/CHS-345R, respectively (Damm et al. 2012; Moriwaki et al. 2003). The sequences of the PCR products were deposited in GenBank with accession numbers MT845879 (ITS), MT861006 (GADPH), MT861007 (ACT), and MT861008 (CHS-1). BLAST searches of the obtained sequences of the ITS, GADPH, ACT, and CHS-1 genes revealed 100% (554/554 nucleotides), 100% (245/245 nucleotides), 97.43% (265/272 nucleotides), and 99.64% (279/280 nucleotides) homology with those of C. boninense in GenBank (JQ005160, JQ005247, JQ005508, and JQ005334, respectively). Phylogenetic analysis (MEGA 6.0) using the maximum likelihood method placed the isolate GZUMH01 in a well-supported cluster with C. boninense. The pathogen was thus identified as C. boninense based on its morphological and molecular characteristics. To our knowledge, this is the first report of the anthracnose disease on R. chinensis caused by C. boninense in the world.