Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design.

Recent advances in cancer immunotherapy have highlighted the potential of neoantigen-based vaccines. However, the design of such vaccines is hindered by the possibility of weak binding affinity between the peptides and the patient's specific human leukocyte antigen (HLA) alleles, which may not elicit a robust adaptive immune response. Triggering cross-immunity by utilizing peptide mutations that have enhanced binding affinity to target HLA molecules, while preserving their homology with the original one, can be a promising avenue for neoantigen vaccine design. In this study, we introduced UltraMutate, a novel algorithm that combines Reinforcement Learning and Monte Carlo Tree Search, which identifies peptide mutations that not only exhibit enhanced binding affinities to target HLA molecules but also retains a high degree of homology with the original neoantigen. UltraMutate outperformed existing state-of-the-art methods in identifying affinity-enhancing mutations in an independent test set consisting of 3660 peptide-HLA pairs. UltraMutate further showed its applicability in the design of peptide vaccines for Human Papillomavirus and Human Cytomegalovirus, demonstrating its potential as a promising tool in the advancement of personalized immunotherapy.

HLA-A+ tertiary lymphoid structures with reactivated tumor infiltrating lymphocytes are associated with a positive immunotherapy response in esophageal squamous cell carcinoma.

BACKGROUND: Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. However, the overall response rate to ICB therapy remains low in esophageal squamous cell carcinoma (ESCC). This study aimed to identify biomarkers of ICB therapy for ESCC and interrogate its potential clinical relevance. METHODS: We investigated gene expression in 42 treatment-naïve ESCC tumor tissues and identified differentially expressed genes, tumor-infiltrating lymphocytes and immune-related genes signatures associated with differential immunotherapy responses. We systematically assessed the tumor microenvironment using the NanoString GeoMx digital spatial profiler, single-cell RNA-seq and multiplex immunohistochemistry in ESCC. Finally, we evaluated the associations between HLA-A-positive tertiary lymphoid structures (TLSs) and patients' responses to ICB in 60 ESCC patients. RESULTS: Tumor infiltrating B lymphocytes and several immune-related gene signatures, such as the antigen presenting machinery (APM) signature, are significantly elevated in ICB treatment responders. Multiplex immunohistochemistry identified the presence of HLA-A+ TLSs and showed that TLS-resident cells increasingly express HLA-A as TLSs mature. Most TLS-resident HLA-A+ cells are tumor-infiltrating T (TIL-T) or tumor-infiltrating B (TIL-B) lymphocytes. Digital spatial profiling of spatially distinct TIL-T lymphocytes and single-cell RNA-seq data from 60 ESCC tumor tissues revealed that CXCL13-expressing exhausted TIL-Ts inside TLSs are reactivated with elevated expression of the APM signature as TLSs mature. Finally, we demonstrated that HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, are associated with a clinical benefit from ICB treatment for ESCC. CONCLUSIONS: HLA-A+ TLSs are present in ESCC tumor tissues. TLS-resident TIL-Ts with elevated expression of the APM signature may be reactivated. HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, may serve as biomarkers for ICB-treated ESCC patients.

Realization of an autonomously controllable process for atomic layer deposition and its encapsulation application in flexible organic light-emitting diodes.

Atomic layer deposition (ALD), an emerging method of thin film fabrication, has recently witnessed a surge of applications in the optoelectronics field. However, reliable processes capable of controlling film composition have yet to be developed. In this work, the effect of precursor partial pressure and steric hindrance on the surface activity was presented and analyzed in detail, which led to the development of a component tailoring process for ALD composition control in intralayer for the first time. Further, a homogeneous organic/inorganic hybrid film was successfully grown. The component unit of the hybrid film under the joint action of EG and O plasma could achieve arbitrary ratios by controlling the EG/O plasma surface reaction ratio via varied partial pressures. Film growth parameters (growth rate per cycle and mass gain per cycle) and physical properties (density, refractive index, residual stress, transmission, and surface morphology) could be modulated as desired. Moreover, the hybrid film with low residual stress was effectively used in the encapsulation of flexible organic light-emitting diodes (OLEDs). Such a component tailoring process is an important step forward in ALD technology, and allowing for in-situ control of thin film components at the atomic level in intralayer.

The rational design of high-performance graphene-based single-atom electrocatalysts for the ORR using machine learning.

In this work, high-performance two-dimensional (2D) graphene-based single-atom electrocatalysts (ZZ/ZA-MNxCy) for the oxygen reduction reaction (ORR) were screened out using machine learning (ML). A model was built for the fast prediction of electrocatalysts and two descriptors valence electron correction (VEc) and degree of construction differences (DC) were proposed to improve the accuracy of the model prediction. Two evaluation criteria, high-performance catalyst retention rate rR and high-performance catalyst occupancy rate rO, were proposed to evaluate the accuracy of ML models in high-performance catalyst screening. The addition of VEc and DC in the model could change the mean absolute error (MAEtest) of the test set, the coefficient of determination (R2test) of the test set, rO, and rR from 0.334 V, 0.683, 0.222, and 0.360 to 0.271 V, 0.774, 0.421, and 0.671, respectively. The partially screened potential high-performance ORR electrocatalysts such as ZZ-CoN4 and ZZ-CoN3C1 were also further investigated using a Density Functional Theory (DFT) method, which confirmed the accuracy of the ML model (MAE = 0.157 V, R2 = 0.821).

Complete stress release in monolayer ALD-Al2O3 films based on mechanical equilibrium homeostasis to realize a bending radius of 1 mm.

Low-temperature-deposited, transparent, high-barrier-performance atomic layer deposition (ALD) Al2O3 films are widely utilized to protect organic optoelectronic devices. However, because the internal compression residual stresses result in poor mechanical properties, these films are unable to realize independent encapsulation. In this work, we propose a pre-bending and substrate thermal expansion process to fabricate low-residual-stress ALD-Al2O3 films by multistep adjustment of mechanical equilibrium homeostasis, compare and analyze the key properties of the films to determine the optimal processing conditions, and adjust the surface area differences between the film and the substrate to acquire a flat-bottom encapsulation substrate. Therefore, fewer cracks form in ALD-Al2O3 deposited at 40 °C, and no significant increase in the water-vapor-transmission rate (WVTR) occurred after multiple bending processes at a 3 mm radius. Furthermore, both the bending radius for the first crack generation and crack saturation density were optimal, resulting in excellent mechanical stability, and a bending radius of 1 mm was achieved. Finally, we confirm the feasibility of the monolayer ALD-Al2O3 prepared by our process for applications in OLEDs. The encapsulated OLED maintained 94% of its initial efficiency after 10 days of bending in a harsh environment at 30 °C and 90% relative humidity.

A pilot school-based health center intervention to improve asthma chronic care in high-poverty schools.

OBJECTIVE: To test the feasibility and effectiveness of a multifaceted intervention administered through school-based health centers (SBHCs) to improve asthma control for children in high-poverty schools with not well controlled asthma. METHODS: Students 4-14 years old with persistent asthma were enrolled from three SBHCs. The centers' advanced practice providers received training on evidence-based asthma guidelines. Students randomized to the intervention received directly observed therapy of their asthma controller medication, medication adjustments as needed by the centers' providers, and daily self-management support. Students randomized to usual care were referred back to their primary care provider (PCP) for routine asthma care. RESULTS: We enrolled 29 students. Students in the intervention group received their controller medication 92% of days they were in school. Ninety-four percent of follow-up assessments were completed. During the study, 11 of 12 intervention students had a step-up in medication; 2 of 15 usual care students were stepped up by their PCP. Asthma Control Test scores did not differ between groups, although there were significant improvements from baseline to the 7 month follow-up within each group (both p < .01). Both FEV1% predicted and FEV1/FVC ratio significantly worsened in the usual care group (both p = .001), but did not change in the intervention group (p = .76 and .28 respectively). CONCLUSIONS: Our pilot data suggest that a multifaceted intervention can be feasibly administered through SBHCs in communities with health disparities. Despite the small sample size, spirometry detected advantages in the intervention group. Further study is needed to optimize the intervention and evaluate outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03032744.

What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism.

Sesquiterpene lactones (STLs) and diterpene lactones (DTLs) are two groups of common phytochemicals with similar structures. It's frequently reported that both exhibit changeable pharmacokinetics (PK) in vivo, especially the unstable absorption and extensive metabolism. However, the recognition of their PK characteristics is still scattered. In this review, representative STLs (atractylenolides, alantolactone, costunolide, artemisinin, etc.) and DTLs (ginkgolides, andrographolide, diosbulbins, triptolide, etc.) as typical cases are discussed in detail. We show how the differences of treatment regimens and subjects alter the PK of STLs and DTLs, with emphasis on the effects from absorption and metabolism. These compounds tend to be quite permeable in intestinal epithelium, but gastrointestinal pH and efflux transporters (represented by P-glycoprotein) have great impact and result in the unstable absorption. As the only characteristic functional moiety, the metabolic behavior of lactone ring is not dominant. The α, ß-unsaturated lactone moiety has the strongest metabolic activity. While with the increase of low-activity saturated lactone moieties, the metabolism is led by other groups more easily. The phase I (oxidation, reduction and hydrolysis reaction) and II metabolism (conjugation reaction) are both extensive. CYP450s, mainly CYP3A4, are largely involved in biotransformation. However, only UGTs (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) has been mentioned in studies about phase II metabolic enzymes. Our work offers a beneficial reference for promoting the safety evaluation and maximizing the utilization of STLs and DTLs.

Overexpression of a methyl-CpG-binding protein gene OsMBD707 leads to larger tiller angles and reduced photoperiod sensitivity in rice.

BACKGROUND: Methyl-CpG-binding domain (MBD) proteins play important roles in epigenetic gene regulation, and have diverse molecular, cellular, and biological functions in plants. MBD proteins have been functionally characterized in various plant species, including Arabidopsis, wheat, maize, and tomato. In rice, 17 sequences were bioinformatically predicted as putative MBD proteins. However, very little is known regarding the function of MBD proteins in rice. RESULTS: We explored the expression patterns of the rice OsMBD family genes and identified 13 OsMBDs with active expression in various rice tissues. We further characterized the function of a rice class I MBD protein OsMBD707, and demonstrated that OsMBD707 is constitutively expressed and localized in the nucleus. Transgenic rice overexpressing OsMBD707 displayed larger tiller angles and reduced photoperiod sensitivity-delayed flowering under short day (SD) and early flowering under long day (LD). RNA-seq analysis revealed that overexpression of OsMBD707 led to reduced photoperiod sensitivity in rice and to expression changes in flowering regulator genes in the Ehd1-Hd3a/RFT1 pathway. CONCLUSION: The results of this study suggested that OsMBD707 plays important roles in rice growth and development, and should lead to further studies on the functions of OsMBD proteins in growth, development, or other molecular, cellular, and biological processes in rice.

Simultaneous determination of six glycosidic aroma precursors in pomelo by ultra-high performance liquid chromatography-tandem mass spectrometry.

An ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the simultaneous determination of six glycosidic aroma precursors in pomelo, including geraniol ß-glucoside, geraniol ß-primeveroside, linalool ß-primeveroside, benzyl ß-primeveroside, 2-phenylethyl ß-primeveroside and nerolidol ß-primeveroside. The results showed that the proposed method has the advantages of rapidity, high sensitivity, and good accuracy. Six glycosidic aroma precursors were effectively separated in a short run time (13 min), and the limit of detection, limit of quantification, recovery, and repeatability of analytes were 0.321-4.47 ng mL-1, 1.07-14.9 ng mL-1, 94.4-109.1%, and 5.2-14.5%, respectively. The developed method was applied to analyze the contents of glycosidic aroma precursors in different organs of pomelo plant, including leaves, flowers and fruits. The analytical result showed that glycosidic aroma precursor contents in plant leaves, flowers and fruits were in the range of 0-5964.9 µg kg-1, and more glycosidic aroma precursors were found in flowers than in leaves or fruits. It is envisioned that the proposed UPLC-MS/MS method have promising application in qualifying and quantifying these six glycosidic aroma precursors in pomelo.

Complete genome sequence of a new achyranthes virus A isolate from Achyranthes bidentata in China.

We have determined the complete genomic sequence of a potyvirus from Achyranthes bidentata in Zhejiang, China, using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) PCR. The genomic RNA is 9482 nucleotides (nt) long excluding the 3'-terminal poly(A) tail and encodes a putative large polyprotein with 3073 amino acids (aa). It has 75.4-53.5% nt sequence identity and 84.0-49.1% polyprotein sequence identity to other potyviruses and is probably a distantly related isolate of the same species as the recently reported achyranthes virus A isolate from South Korea (AcVA-SK). This is the first report of the occurrence of a potyvirus infecting A. bidentata in China.

Tumor microenvironment-activated cancer cell membrane-liposome hybrid nanoparticle-mediated synergistic metabolic therapy and chemotherapy for non-small cell lung cancer.

BACKGROUND: Biomimetic nanotechnology-based RNA interference (RNAi) has been successful in improving theranostic efficacy in malignant tumors. Its integration with hybrid biomimetic membranes made of natural cell membranes fused with liposomal membranes is mutually beneficial and extends their biofunctions. However, limited research has focused on engineering such biomimetics to endow them with unique properties and functions, in particular, those essential for a "smart" drug delivery system, such as a tumor microenvironment (TME)-activated multifunctional biomimetic nanoplatform. RESULTS: Herein, we utilized an integrated hybrid nanovesicle composed of cancer cell membranes (Cm) and matrix metallopeptidase 9 (MMP-9)-switchable peptide-based charge-reversal liposome membranes (Lipm) to coat lipoic acid-modified polypeptides (LC) co-loaded with phosphoglycerate mutase 1 (PGAM1) siRNA (siPGAM1) and DTX. The nanovesicle presented a negatively charged coating (citraconic anhydride-grafted poly-L-lysine, PC) in the middle layer for pH-triggered charge conversion functionalization. The established chemotherapeutic drug (DTX) co-delivery system CLip-PC@CO-LC nanoparticles (NPs) have a particle size of ~ 193 nm and present the same surface proteins as the Cm. Confocal microscopy and flow cytometry results indicated a greater uptake of MMP-9-treated CLip-PC@CO-LC NPs compared with that of the CLip-PC@CO-LC NPs without MMP-9 pretreatment. The exposure to MMP-9 activated positively charged cell-penetrating peptides on the surface of the hybrid nanovesicles. Moreover, pH triggered membrane disruption, and redox triggered DTX and siRNA release, leading to highly potent target-gene silencing in glycolysis and chemotherapy with enhanced antiproliferation ability. The biodistribution results demonstrated that the CLip-PC@LC-DiR NPs accumulated in the tumor owing to a combination of long blood retention time, homologous targeting ability, and TME-activated characteristics. The CLip-PC@CO-LC NPs led to more effective tumor growth inhibition than the DTX and free siPGAM1 formulations. CONCLUSIONS: TME-activated cancer cell membrane-liposome integrated hybrid NPs provide an encouraging nanoplatform that combines RNAi with chemotherapy for precise treatment of non-small cell lung cancer.

Gynura japonica: A new host of Apple stem grooving virus and Chrysanthemum virus B in China.

Gynura japonica (Thunb.) Juel [Asteraceae; syn: G. segetum (Lour.) Merr] is an important perennial medicinal herb used in China for topical treatment of trauma injuries (Lin et al. 2003). It grows naturally in the southern provinces of China and is also sometimes cultivated. During 2018-2020, wild G. japonica plants exhibiting chlorotic spots and mosaic symptoms were observed in Zhejiang province, China. To identify the possible causal agents of the disease, a single symptomatic leaf sample was collected in August 2019 and sent to Zhejiang Academy of Agricultural Sciences (Hangzhou, China) for next generation sequencing (NGS). Total RNAs extracted with TRIzol (Invitrogen, Carlsbad, USA) were subjected to high throughput sequencing on the Illumina NovaSeq 6000 platform with PE150bp and data analysis was performed by CLC Genomic Workbench 11 with default parameters (QIAGEN, Hilden, Germany). A total of 37,314,080 paired-end reads were obtained, and 11,785 contigs (961 to 10,964 bp) were generated and compared with sequences in GenBank using BLASTn or BLASTx. Of the total of 12 viral-related contigs obtained, one with a length of 6,442 nt mapped to the genomic RNA of ASGV (MN495979), seven contigs with lengths ranging from 1,034 to 2,901 nt mapped to Chrysanthemum virus B (CVB), and four mapped to broad bean wilt virus 2 (BBWV2), a virus which is known to infect G. procumbens (Kwak et al. 2017). To further confirm the presence of ASGV and CVB, primers were designed and the complete nucleotide sequences of both viruses were amplified from the original NGS sample using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) according to the manufacturer's instructions (Tiosbio, Beijing, China). BLASTn analysis revealed that the complete 6,451 nt sequence of ASGV (GenBank accession No. MW259059) shared the highest identity (81.2%) with a Chinese isolate of ASGV from citrus (MN495979). The two isolates grouped with another Chinese isolate (from pear) in phylogenetic analysis. The predicted coat protein of the virus had the highest nt identity of 93.7% (96.2% amino acid sequence identity) with that of the Chinese ASGV isolate XY from apple (KX686100). The complete genomes of two distinct molecular variants of CVB (both 8,987 nt in length) were also obtained from this sample (GenBank accession Nos. MW269552, MW269553). They shared 86.8% nt identity with each other and had 81.1% and 82.1% identity to the only known complete sequence of CVB from chrysanthemum (AB245142). Ten additional wild G. japonica plants with mosaic symptoms were collected randomly during 2019-2020 from Hangzhou (n=6) and Ningbo (n=4) in Zhejiang province and tested by RT-PCR with specific primer pairs to detect BBWV2, ASGV and CVB. RT-PCR and subsequent sequencing revealed that these three viruses were present in all the samples tested, indicating that co-infection of G. japonica by ASGV, CVB and BBWV2 is common. CVB mainly infects chrysanthemum (Singh et al. 2012), while ASGV is known as a pathogen of various fruit trees especially in the family Rosaceae, although there are recent reports that it can also infect some plants in Gramineae, Asparagaceae and Nelumbonaceae (Bhardwaj et al. 2017; Chen et al. 2019; He et al. 2019). Our results provide the first report that Gynura is a natural host of CVB and ASGV. Further surveys and biological studies are underway to evaluate the importance of Gynura as a virus reservoir for epidemics among the various hosts.

A prospective study of Salvia miltiorrhiza and Rhizoma chuanxiong preparation in the treatment of hypoparathyroidism after total thyroidectomy.

This study aimed to investigate the clinical efficacy of Salvia miltiorrhiza and Rhizoma chuanxiong preparation on hypoparathyroidism. A total of 100 patients with hypoparathyroidism after total thyroidectomy were erolled, they were divided into the observation group (n=50), Salvia miltiorrhiza and Rhizoma chuanxiong preparation were added on the basis of traditional treatment. The control group (n=50), were treated with traditional treatment. To analyze the therapeutic effect of Salvia miltiorrhiza and Rhizoma chuanxiong preparation on hypoparathyroidism. After follow-up, the recovery time of parathyroid function in the observation group was significantly shorter than the control (P<0.05). No permanent hypoparathyroidism in the observation group and 4 cases in the control, which was statistically significant (P<0.05). The serum PTH in the observation group was significantly higher than the control on the 7th, 30th day, 3rd and 6th month. The level of serum calcium in the observation group was significantly higher than the control on the 3rd, 7th and 30th day (P<0.05). Salvia miltiorrhiza and Rhizoma chuanxiong preparation has obvious effects on the treatment of hypoparathyroidism and has low adverse reactions, which is worthy of clinical application.

Rapid and visual detection of milk vetch dwarf virus using recombinase polymerase amplification combined with lateral flow strips.

BACKGROUND: Milk vetch dwarf virus (MDV) is an important ssDNA virus which causes yellowing, stunting and leaf rolling symptoms on legumes. In China, the virus causes great economic losses and has recently been found to infect tobacco. The expansion of its host range and its ability to spread rapidly has given rise to the urgent need for a sensitive, specific and rapid diagnostic assay that can assist in effective disease control. METHODS: Assays based on the polymerase chain reaction combined with lateral flow strip detection (PCR-LFS) and recombinase polymerase amplification combined with LFS (RPA-LFS) were developed targeting the coat protein (CP) gene of MDV. RESULTS: The PCR and RPA assays could detect respectively 103 copies or 101 copies of MDV by agarose gel electrophoresis. The PCR-LFS and RPA-LFS assays developed could both detect as few as 101 copies per reaction at 37 °C. Both methods could detect MDV in crude leaf extracts. CONCLUSIONS: The RPA-LFS assay developed is a rapid, sensitive and specific method for detecting MDV, which is convenient and has great potential for use in the field.

Predictive Model for Operative Intervention after Blunt Abdominal Trauma in Children with Equivocal CT Findings: A Pilot Study.

BACKGROUND: To study the clinical and radiologic factors predicting the need for surgical intervention after blunt abdominal trauma (BAT) in children with equivocal computed tomography (CT) scan findings. METHODS: We performed a retrospective review of the trauma database at our level I pediatric trauma center between 2011 and 2019. We selected patients with BAT and equivocal findings for surgical intervention on CT scan. We studied five factors: abdominal wall bruising (AWB), abdominal pain/tenderness (APT), thoracolumbar fracture, the presence of free fluid (FF), and the presence of solid organ injury, all previously reported in the literature to predict the need for operative intervention. We used t-test, the Kruskal-Wallis test and logistic regression to study the association of these factors with the need for operation in our pediatric cohort. RESULTS: Of 3044 blunt trauma patients, 288 had abdominal CT scans with 61 patients demonstrating equivocal findings. Operation was performed for 12 patients (19.7%) confirming surgically correctable traumatic injuries. The need for surgical intervention was significantly associated with the age of the patients (P = 0.03), the presence of APT (P = 0.001), AWB (P = 0.01), and FF (P = 0.04). The presence of thoracolumbar fracture and solid organ injury were not significantly associated with the need for operation. For the subset of 37 patients who were injured in a motor vehicle crash, five (13.5%) required surgical intervention, which was significantly associated with the presence of AWB (P = 0.04), APT (P = 0.01), and FF (P = 0.03). A predictive model that used these factors produced a receiver operating characteristic curve of 0.86. CONCLUSIONS: In cases of equivocal abdominal CT scan findings to evaluate BAT in children, the presence of abdominal wall tenderness, AWB, or FF may be significant factors predicting more accurately the need for operative intervention. A predictive model using the combination of clinical and image findings might determine with more certainty, the need for surgical intervention in children with BAT and equivocal CT findings. Validation on a larger multi-institutional data set should be done.

Quality assessment and differentiation of Aucklandiae Radix and Vladimiriae Radix based on GC-MS fingerprint and chemometrics analysis: basis for clinical application.

Vladimiriae Radix, a geo-authentic medicinal herb found in Sichuan Province in China, is highly similar in chemical composition and pharmacological activity to Aucklandiae Radix. It is often used in local practice and as a substitute for Aucklandiae Radix in the treatment of gastrointestinal tract diseases. However, Vladimiriae Radix is preferred to Aucklandiae Radix in traditional Chinese medicine in Sichuan. In order to compare the difference in quality between the two species and differentiate them according to their chemical profiles, and further to explain the rationality of using Vladimiriae Radix as a substitute and explore the reason for the medication preference in Sichuan, similarity was evaluated using gas chromatography-mass spectrometry (GC-MS) fingerprinting and chemometric analysis. Volatile compounds were identified by comparing mass spectra with spectral data from the National Institute of Standards and Technology library 14.L (NIST 14.L) and the linear retention indices (RI) with those previously reported. The results showed that the similarity between the samples from Aucklandiae Radix (>96%) was greater than that of Vladimiriae Radix (>80%). In addition, 41 and 38 compounds were identified in 10 batches of Vladimiriae Radix and Aucklandiae Radix, respectively, and 21 compounds were common to both species, of which dehydrocostus lactone and aplotaxene were abundant in both. However, γ-patchoulene, longicyclene, ß-gurjunene, humulene1,2-epoxide, and ß-patchoulene were unique to Vladimiriae Radix, while 4-terpineol, α-ionone, trans-α-bergamotene, γ-selinene, and camphene were characteristic compounds of Aucklandiae Radix. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested that the two species were well differentiated with regard to the level of essential oils. Orthogonal partial least squares discriminant analysis (OPLS-DA) further showed that compounds including costol, aplotaxene, caryophyllene, humulene, and ß-eudesmol, together with the characteristic compounds of the two species, could be regarded as potential markers for differentiation, among which ß-eudesmol, which is richer in Vladimiriae Radix, and ß-patchoulene, which is unique to Vladimiriae Radix, have potential therapeutic effects on gastrointestinal diseases. The results obtained in this study distinguished Vladimiriae Radix and Aucklandiae Radix on a chemical level, and the similarity in chemical constituents may provide a basis for the rationality of Vladimiriae Radix as a substitute, while ß-patchoulene and ß-eudesmol existing in Vladimiriae Radix provide a theoretical basis for its preferential use in Sichuan. The analysis method established here has important implications for the quality control and differentiation of Vladimiriae Radix and Aucklandiae Radix, which can also serve as a reference for the identification of similar species. Graphical abstract.

Global research trends of adult degenerative scoliosis in this decade (2010-2019): a bibliometric study.

OBJECTIVE: With the population aging, there is an associated rise in the prevalence of adult degenerative scoliosis (ADS). However, limited data were found to elaborate the trend of ADS research. Our study aims to investigate the global trend of ADS research in this decade. METHODS: ADS-related publications from 2010 to 2019 were extracted from the Web of Science and Medline database. Excel 2016, GraphPad Prism 6, and VOSviewer software were adopted to analyze the search results for number of publications, citation, and H-index. RESULTS: A total of 1282 papers were included and were cited 16,770 times. The USA accounted for 40.41% of the articles, 60.35% of the citations, and the highest H-index of 51. China ranked second in total number of articles, third in citation frequency (1373), and fourth with an H-index of 18. The journal Spine (IF = 2.903, 2019) had the highest number of publications. Shaffery CI published the most articles in this field (40). Key words of ADS research were classified into three clusters: "Surgical technique," "Mechanism," and "Radiological parameter." The "Radiological parameter" cluster became the most popular, and it came with the latest hot spots of "slope," "cervical lordosis," "mismatch," and "PI-LL." CONCLUSION: Literature growth in ADS was rapidly expanding in this decade. The USA was the most productive country and also had a largest quantity of top authors and institutes, so that scholars can keep following and cooperated with. Radiological parameter was an emerging topic and might also be a hot spot in the near future.

Adapted nano-carriers for gastrointestinal defense components: surface strategies and challenges.

Nano-carriers (NCs) provide drugs with protective and oriented strategies. Despite their success in parenteral administration, NCs still need to be optimized to meet the more serious obstacles encountered in the gastrointestinal tract (GIT). The main defense mechanisms include renewing mucus, epithelial obstacles and digestion by GIT segments. These hurdles pose challenges even before NCs target molecules or proteins, which has often led to unsatisfactory delivery efficiency. Therefore, a critical focus is the exemption from negative effects of GIT. A series of adapted NCs have been designed based on surface strategies to form an expected distribution and increase gastrointestinal utilization. In this paper, we review the strategies and efforts of NCs to adapt to gastrointestinal defense components, including the mucus, epithelium and gastrointestinal segments; the related gastrointestinal mechanisms and functions are also summarized synchronously. Last, we discuss the delivery challenges in terms of physiopathological GIT and surface properties of the NCs.

Perceptions of monogamy, nonconsensual nonmonogamy and consensual nonmonogamy at the intersections of race and gender.

Given the historical entrenchment of racialised stereotypes of Black women and Black men as sexually promiscuous, we wondered whether consensual nonmonogamy (CNM) among Black partners would be seen as favourably as among white partners. We also wondered if Black participants would perceive different relationship types differently from white participants. We pursued these questions in a vignette study featuring heterosexual couples coded as Black or as white and engaged in three different relationship types: monogamy, nonconsensual nonmonogamy (NCNM) and CNM. To facilitate comparisons across race*gender intersections, we used a sample comprising equivalent numbers of Black women, white women, Black men and white men aged 18-40. Contrary to expectations, analyses did not offer evidence of a racialised sexual double standard insofar as participant perceptions of relationship quality did not differ when considering a Black couple or a white couple. Indicating the persistence of mononormativity, participants across race*gender subsamples perceived monogamous relationships to be of higher quality, regardless of the vignette couple's race. We also found Black women, Black men and white women perceived CNM more favourably than NCNM, while there was no differentiation between CNM and NCNM among white men.

Exploring the Distribution of Blast Resistance Alleles at the Pi2/9 Locus in Major Rice-Producing Areas of China by a Novel Indel Marker.

Rice blast disease caused by the fungus Magnaporthe oryzae damages cereal crops and poses a high risk to rice production around the world. Currently, planting cultivars with resistance (R) genes is still the most environment-friendly approach to control this disease. Effective identification of R genes existing in diverse rice cultivars is important for understanding the distribution of R genes and predicting their contribution to resistance against blast isolates in regional breeding. Here, we developed a new insertion/deletion (InDel) marker, Pigm/2/9InDel, that can differentiate the cloned R genes (Pigm, Pi9, and Pi2/Piz-t) at the Pi2/9 locus. Pigm/2/9InDel combined with the marker Pi2-LRR for Pi2 was applied to determine the distribution of these four R genes among 905 rice varieties, most of which were collected from the major rice-producing regions in China. In brief, nine Pigm-containing varieties from Fujian and Guangdong provinces were identified. All of the 62 Pi2-containing varieties were collected from Guangdong, and 60 varieties containing Piz-t were from seven provinces. However, Pi9 was not found in any of the Chinese varieties. The newly identified varieties carrying the Pi2/9 alleles were further subjected to inoculation tests with regional blast isolates and field trials. Our results indicate that Pigm and Pi2 alleles have been introgressed for blast resistance breeding mainly in the Fujian and Guangdong region, and Pi9 is a valuable blast resistance resource to be introduced into China.