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Tordyliopsis is a monotypic genus within the family Apiaceae and is endemic to the southern margin of the Himalayas. The type species, Tordyliopsis brunonis, is easily distinguished by its lanceolate bracts and bracteoles. In this study, we used both phylogenetic and morphological analyses to investigate the relationship between T. brunonis and other species in the Apiaceae. Our phylogenetic analyses of ITS sequences and 79 coding sequences from complete plastid genomes revealed that T. brunonis is nested with Semenovia species. Additionally, our morphological analysis showed that Tordyliopsis and Semenovia share several similar features, including elliptic or oblong mericarps with widely spaced dorsal ribs, broader and winged marginal ribs with slightly inflated distal parts, clavate vittae, and domed stylopodium. Based on these results, we propose that the monotypic genus Tordyliopsis should be transferred to Semenovia.

Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder.468 participants received 2 TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality.The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% versus 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram.TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression. This article is protected by copyright. All rights reserved.

Neuroinflammation results in neuropathic pain following brachial plexus avulsion (BPA). This research was designed for investigating the function of miR-506-3p in BPA-induced neuropathic pain (NP). A total brachial plexus root avulsion (tBPRA) model was produced in adult rats as well as IL-1β-treated motoneuron-like NSC-34 cells and the LPS-treated microglia cell line BV2 for in vivo and in vitro experiments, respectively. RT-PCR and western blot were performed to detect the profiles of miR-506-3p, CCL2 and CCR2, NF-κB, FOXO3a, TNF-α, IL-1β, and IL-6 in cells or the spinal cord close to the tBPI lesion. Neuronal apoptosis was evaluated by immunohistochemistry (IHC) in vivo. CCK8, TUNEL staining, and the LDH kit were adopted for the evaluation of neuronal viability or damage in vitro. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays analyzed the targeted association between miR-506-3p and CCL2. As shown by the data, miR-506-3p was vigorously less expressed, while CCL2-CCR2, NF-κB TNF-α, IL-1β, and IL-6 were up-regulated in the spinal cord with tBPI. Overexpression of miR-506-3p attenuated neuronal apoptosis and microglial inflammation. Mechanistically, CCL2 was a downstream target of miR-506-3p. Up-regulating miR-506-3p dampened CCL2-CCR2 and NF-κB activation in the spinal cord and microglia. miR-506-3p had neuroprotective and inflammation-fighting functions in the tBPI rat model via CCL2/CCR2/NF-κB axis.

The significance of postoperative adjuvant radiotherapy (PORT) on the survival of resected IIIA-N2 non-small cell lung cancer (NSCLC) remains controversial. Here, we aimed to determine the predictive value of the three nodal classifications which might aid in PORT decision-making.A total of 4797 patients with stage IIIA-N2 resected NSCLC were identified in the Surveillance, Epidemiology and End Results (SEER) database and were grouped by whether PORT was administered. Survival analysis was used to identify the patient groups who can benefit from PORT. Multivariate analysis was performed to confirm the independent risk factors for lung cancer-specific survival (LCSS) and overall survival (OS). A validation cohort of 1184 patients from three medical centers in China were also included.PORT was not associated with better LCSS and OS in the entire cohort after propensity score matching (PSM). However, in the subgroups of positive lymph nodes 4 (PLN4), lymph node ratio 4 (LNR4), and log odds of positive lymph nodes 4 (LODDS4), PORT exhibited its role in improving LCSS (p lt; 0.05). Although the three nodal classifications were all identified as independent predictors of LCSS and OS, LODDS classification had the best discriminatory ability and prognostic accuracy for stage IIIA-N2 patients. Similar results were also obtained in the validation cohort.The LODDS classification not only exhibited the best prognostic performance in predicting LCSS and OS in stage IIIA-N2 disease, but also could help tailor individualized PORT.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increasing in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

The self-weight of solid waste or machine-rolled compaction can induce or trigger contaminant migration in the landfill. Although the consolidation-induced hydraulic gradient driving solution transport has been extensively investigated, little attention has been paid to ion migration caused by its concentration gradient variation. It is necessary to more precisely predict the multi-stage contaminant transports in deforming porous material. Based on the modified Cam-clay model, the proposed fluid-solid coupled model can simulate the elastoplastic deformation behavior of layered kaolinite and KBr solution transport/sorption, and its modeling results were validated by published laboratory data. The solid-fluid interactions were analyzed by comparing various transport manners of K+ and Br− from excess pore pressure generation to dissipation. Results reveal that the consolidation process can accelerate KBr solute advection from the contaminated layer into the uncontaminated layer, and then affects the subsequent diffusion, mechanical dispersion and sorption for K+ and Br−. The simulations also indicate that consolidation-induced solute transport is time-dependent, and therefore the ion diffusion and mechanical dispersion should receive more attention. © 2021 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ).

Lung adenocarcinoma (LUAD) is one of the most common malignancies worldwide. Combination chemotherapy with cisplatin (CDDP) plus pemetrexed (PEM) remains the predominant therapeutic regimen; however, chemoresistance greatly limits its curative potential. Here, through CRISPR-Cas9 screening, we identified miR-6077 as a key driver of CDDP/PEM resistance in LUAD. Functional experiments verified that ectopic overexpression of miR-6077 desensitized LUAD cells to CDDP/PEM in both cell lines and patient-derived xenograft models. Through RNA sequencing in cells and single-cell sequencing of samples from patients with CDDP/PEM treatments, we observed CDDP/PEM-induced upregulation of CDKN1A and KEAP1, which in turn activated cell-cycle arrest and ferroptosis, respectively, thus leading to cell death. Through miRNA pull-down, we identified and validated that miR-6077 targets CDKN1A and KEAP1. Furthermore, we demonstrated that miR-6077 protects LUAD cells from cell death induced by CDDP/PEM via CDKN1A-CDK1-mediated cell-cycle arrest and KEAP1-NRF2-SLC7A11/NQO1-mediated ferroptosis, thus resulting in chemoresistance in multiple LUAD cells both

The exploration of real-world cooperative behavior is essential for societal development. In real life, the surrounding social environment and past experiences often influence individuals’ assessment of their self-fitness. Based on this phenomenon, we propose a novel model that explores the effect of subjective human perceptions on the evolution of cooperation, combining temporal and spatial dimensions into individual fitness. In this model, strategy persistence is used as a proxy for the temporal dimension. Strategy popularity, on the other hand, is portrayed to characterize the subjective influence of the spatial dimension. The weight distribution between the temporal perception and the spatial perception can be controlled by the parameter α, and the intensity of the subjective perception can be regulated by the parameter β. Numerical experiments show that when spatial perception is fully considered, the system tends to reach a fully cooperative state via network reciprocity. Conversely, fully considering the temporal state allows some cooperators to maintain cooperative behavior even under more unfavorable conditions (i.e., larger temptation). Notably, an intermediate state α exists when both temporal and spatial perceptions are considered, resulting in a higher level of cooperation compared to α = 0 or 1. Micro-analysis of the evolution of cooperation in temporal or spatial perception has been investigated to reveal the mechanism of macroscopic phenomena. Additionally, the robustness of the mechanism is discussed by varying the intensity of subjective perception β and the upper limit of strategy age Amax. Similarly, we explore the validity of our work to different network structures, the different numbers of agents, and the real social network. Overall, this study contributes to understanding the impact of individual subjective factors, such as temporal-spatial perception, on the evolution of cooperation in society.

Airborne forward-looking radar (AFLR) has been more and more impoatant due to its wide application in the military and civilian fields, such as automatic driving, sea surveillance, airport surveillance and guidance. Recently, sparse deconvolution technique has been paid much attention in AFLR. However, the azimuth resolution performance gradually decreases with the complexity of the imaging scene. In this paper, a data-driven airborne Bayesian forward-looking superresolution imaging algorithm based on generalized gaussian distribution (GGD- Bayesian) for complex imaging scene is proposed. The generalized gaussian distribution is utilized to describe the sparsity information of the imaging scene, which is quite essential to adaptively fit different imaging scenes. Moreover, the mathematical model for forward-looking imaging was established under the maximum a posteriori (MAP) criterion based on the Bayesian framework. To solve the above optimization problem, quasi-Newton algorithm is derived and used. The main contribution of the paper is the automatic selection for the sparsity parameter in the process of forward-looking imaging. The performance assessment with simulated data has demonstrated the effectiveness of our proposed GGD- Bayesian algorithm under complex scenarios.

Semenovia brunonis (DC.) X.L.Guo, Q.Y.Xiao & X.J.He com. nov. (Fig.3, 4) Basionym: Tordyliopsis brunonis DC. (1830: 199) Taxonomic synonym: Heracleum brunonis (DC.) C. B. Clarke (1879: 713) Type: INDIA. In Kamaon Nepaliae versus Emodum, Blinkworth 590 (lectotype: G-DC, designated by Watson (1998); isolectotypes: BM000944789, BM000944790, E00002937, K000075516, K000075517). Recognition: Semenovia brunonis is characterized by having oblong-ovate ultimate segments with irregularly serrate margin and acute apex, rays with densely softly pubescent, lanceolate-acuminate bracts and bracteoles, elliptic or oblong and pubescent mericarps with well-developed marginal ribs, unobvious medium and lateral ribs, clavate vittae, and domed stylopodium. Distribution and habitat: One population of Semenovia brunonis was detected in Yadong County in Xizang, China. Further, it was also found in Nepal, Bhutan, and India. S. brunonis usually inhabits an alpine bush at an altitude of ca. 4200 m in China., Published as part of Guo, Xian-Lin, Xiao, Qun-Ying, Gou, Wei, Zhou, Song-Dong & He, Xing-Jin, 2023, Morphological and phylogenetic evidence for the transfer of the monotypic genus Tordyliopsis to Semenovia (Apiaceae), pp. 63-72 in Phytotaxa 597 (1) on page 70, DOI: 10.11646/phytotaxa.597.1.7, http://zenodo.org/record/7918814, {"references":["Clarke, C. B. (1879) Umbelliferae. In: Hooker, J. D. (ed.) Flora of British India, London, pp. 665 - 720.","Watson, M. F. (1998) Notes relating to the flora of Bhutan: XXXIII. Umbelliferae, I. Edinburgh Journal of Botany 53: 127 - 144."]}

Ligusticopsis miyiensis (Franch.) J.Q. Lei & X.J. He, comb. nov. (Figs. 1, 2). ≡ Ligusticum glaucescens Franch. (1894: 134). non Ligusticopsis glaucescens (H.Wolff) Lavrova & Kljuykov in Kljuykov & Lavrova (1994: 105) [≡ Pleurospermum glaucescens H. Wolff (1929: 114)] Type:— CHINA. Yunnan: in pratis adumbratis prope Mo-che-tschin, ad cataractas supra Tapin-tze, 03 Oct 1882, Delavay (syntype P!: P03224789, P03224792, P03224793, P03224794, P03224795); Yunnan: in pratis montis Pee-ngaytze, supra Tapin-tze, 01 Sep 1882, Delavay 446 (lectotype P!: P03224790, designated by Pimenov 2017). Description:— Perennial herbs. Plants 40–80 cm. Roots cylindric, thin. Stems erect, hollow, glabrous, striate, base clothed in fibrous remnant sheaths. Basal petioles 2–6 cm, with ovate sheaths, rachis densely pilose; blade ovatetriangular, 10–12 × 8–10 cm, 2-pinnate, primary pinnae 3–4 pairs, coriaceous; ultimate segments lanceolate, ca. 3– 5 × 1–1.5 mm, apex apiculate. Cauline leaves sessile, sheathing, blade similar to basal, reduced. Umbels terminal and lateral, 4–6 cm across; bracts 3–6, linear, entire, rarely apex 3-lobed or pinnate, marginal white membranous, caducous; rays 16–24, subequal, 2–4 cm, inner faces scabrous; bracteoles 9–11, linear, entire, rarely apex 3-lobed or pinnate, marginal white membranous, longer than umbellules. Calyx teeth conspicuous, subulate, ca. 0.3 mm. Petals white, obcordate, base cuneate. Styles longer than stylopodium; stylopodium conical. Fruit oblong, ca. 4.5 × 3.5 mm, glabrous, strongly compress dorsally; dorsal ribs filiform, slightly prominent, marginal ribs winged, wings ca. 0.8 mm; vittae 1–2 in each furrow, 4–6 on commissure. Seed face plane. Phenology:— The species was found flowering in September to October, fruiting in October to November. Diagnosis:— Ligusticopsis miyiensis is most similar to five validated Ligusticopsis species, being Ligusticopsis capillacea, Ligusticopsis hispida, Ligusticopsis modesta, Ligusticopsis scapiformis and Ligusticopsis brachyloba. However, Ligusticopsis miyiensis differed from them in having 2-pinnate leaf blades, ultimate segments of leaves lanceolate, bracts and bracteoles mainly linear, entire, with membranous margins, calyx teeth subulate, and mericarps oblong. Distribution and habitat:— Ligusticopsis miyiensis is distributed in Yunnan (“Pee-ngay-tze” & “Mo-che-tchin, supra Tapin-tze”) and Sichuan (Miyi), China. It grows in hillside grasslands at elevations between 1600 and 2800 m. Additional specimens examined:— CHINA. Yunnan: Zhongdian, Haba, 2800 m, 27°23′N, 100°10′E, 1963, anonymous 068400 (HITBC!). Sichuan: Miyi, Laoyamen, 1845 m, 27°2′33.22″N, 101°57′17.22″E, 10 Oct 2022, J. Q . Lei & J. Cai LC20221010001, LC20221010002, LC20221010003 (SZ!)., Published as part of Lei, Jia-Qing, Cai, Jing, Zhou, Song-Dong & He, Xing-Jin, 2023, Ligusticopsis miyiensis (Apioideae, Apiaceae), a new combination from China revealed by morphological and molecular evidence, pp. 273-282 in Phytotaxa 591 (4) on pages 278-279, DOI: 10.11646/phytotaxa.591.4.4, http://zenodo.org/record/7835539, {"references":["Kljuykov, E. V. & Lavrova, T. V. (1994) On systematic position of some species of the genera Pleurospermum and Trachydium (Umbelliferae). Botanicheskii Zhurnal 79: 102 - 108.","Wolff, K. F. A. H. (1929) Umbelliferae Asiaticae novae relictae descriptae. Repertorium Specierum Novarum Regni Vegetabilis 27: 112 - 128. https: // doi. org / 10.1002 / fedr. 4870270109","Pimenov, M. G. (2017) Updated checklist of Chinese Umbelliferae: nomenclature, synonymy, typification, distribution. Turczaninowia 20: 106 - 239. https: // doi. org / 10.14258 / turczaninowia. 20.2.9"]}

Quantum fluctuations disrupt the cyclic motions of dissipative Kerr solitons (DKSs) in nonlinear optical microresonators and consequently cause timing jitter of the emitted pulse trains. This problem is translated to the performance of several applications that employ DKSs as compact frequency comb sources. Recently, device manufacturing and noise reduction technologies have advanced to unveil the quantum properties of DKSs. Here we investigate the quantum decoherence of DKSs existing in normal-dispersion microresonators known as dark pulses. By virtue of the very large material nonlinearity, we directly observe the quantum decoherence of dark pulses in an AlGaAs-on-insulator microresonator, and the underlying dynamical processes are resolved by injecting stochastic photons into the microresonators. Moreover, phase correlation measurements show that the uniformity of comb spacing of quantum-limited dark pulses is better than 1.2 × 10−16 and 2.5 × 10−13 when normalized to the optical carrier frequencies and repetition frequencies, respectively. Comparing DKSs generated in different material platforms explicitly confirms the advantages of dark pulses over bright solitons in terms of quantum-limited coherence. Our work establishes a critical performance assessment of DKSs, providing guidelines for coherence engineering of chip-scale optical frequency combs.

Background Neoadjuvant chemotherapy (NACT) becomes the first-line option for advanced tumors, while patients who are not sensitive to it may not benefit. Therefore, it is important to screen patients suitable for NACT. Methods Single-cell data of lung adenocarcinoma (LUAD) and esophageal squamous carcinoma (ESCC) before and after cisplatin-containing (CDDP) NACT and cisplatin IC50 data of tumor cell lines were analyzed to establish a CDDP neoadjuvant chemotherapy score (NCS). Differential analysis, GO, KEGG, GSVA and logistic regression models were performed by R. Survival analysis were applied to public databases. siRNA knockdown in A549, PC9, TE1 cell lines, qRT-PCR, western-blot, cck8 and EdU experiments were used for further verification in vitro. Results 485 genes were expressed differentially in tumor cells before and after neoadjuvant treatment for LUAD and ESCC. After combining the CDDP-associated genes, 12 genes, CAV2, PHLDA1, DUSP23, VDAC3, DSG2, SPINT2, SPATS2L, IGFBP3, CD9, ALCAM, PRSS23, PERP, were obtained and formed the NCS score. The higher the score, the more sensitive the patients were to CDDP-NACT. The NCS divided LUAD and ESCC into two groups. Based on differentially expressed genes, a model was constructed to predict the high and low NCS. CAV2, PHLDA1, ALCAM, CD9, IGBP3 and VDAC3 were significantly associated with prognosis. Finally, we demonstrated that the knockdown of CAV2, PHLDA1 and VDAC3 in A549, PC9 and TE1 significantly increased the sensitivity to cisplatin. Conclusions NCS scores and related predictive models for CDDP-NACT were developed and validated to assist in selecting patients who might benefit from it.

Data for the research article ofQuantum decoherence of dark pulses in optical microresonators.

BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cell-based administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intra-articular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163(+) regenerative M2 macrophages over CD86(+) M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION: Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.

Nanoparticle-based chemophotothermal therapy (CPT) is a promising treatment for multidrug resistant tumors. In this study, a drug nanococktail of DIR825@histone was developed by employing doxorubicin (DOX), NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser. After localized intervention, DIR825@histone penetrated tumor tissues by transcytosis, efficiently entered tumor cells and targeted the cell nuclei. DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release. Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting. Moreover, an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury. Therefore, DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors., Graphical abstract Image 1, Highlights • Proposing an interventional nucleus-targeted chemophotothermal therapy (CPT) for treating MDR tumors • Using natural human histones for the first time to fabricate nucleus-targeted nanococktails. • The nanococktail can penetrate tumor tissues by transcytosis, efficiently enter tumor cells and target the cell nuclei. • Highly improved intracellular MDR reversion and less heat shock response in drug-resistant tumor cells can be achieved by nucleus-targeted chemophotothermal therapy. • The combination of the nucleus-targeted DIR825@histone and interventional laser harvested the best therapeutic outcomes against drug-resistant tumor.

Single-cell transcriptomics has been used to investigate various tumors to elucidate the molecular distinction of all cell type compositions of a complex mix.This study aimed to investigate malignant-cell-specific genes to explore diagnostic and therapeutic biomarkers using single-cell transcriptomic data of lung adenocarcinoma.10X single-cell RNA-seq data of fourteen patients with lung adenocarcinoma were analyzed. Genes that expressed differentially and those with higher confidence to distinguish tumor cells from normal cells were picked out using the ROC curves. The LASSO regression method was used to select most markedly correlated genes to predict the malignancy of every single cell within a model. We also conducted further experiments to determine their roles in lung cancer in vitro.Twenty two thousand four hundred and ninety one tumor and 181 666 normal single cells were analyzed where 369 genes were found to be specifically expressed in single malignant cells. Seventy of them, encoding secreted or membrane-bound proteins, showed involvement in cell-to-cell communications in tumor biology. KRT18 and the other six genes were identified as predictors to distinguish single malignant cells and were integrated to construct an accurate (96.1%) predicting model. Notably, IRX2, SPINK13, and CAPN8 outperformed the other four genes. Further experiments confirmed the upregulation of them in lung adenocarcinoma at both tissue and cell levels. Proliferative capacities of lung adenocarcinoma cells were attenuated by knocking-down of either of them. However, targeting CAPN8, IRX2, or SPINK13 hardly exerted a cytotoxic effect on these cells.Apart from the current model, similar tools were still warranted using single-cell RNA-seq data of more types of tumors. The three genes identified as potential therapeutic targets in the present study still need to be validated in more in lung cancer.Our model can aid the analyses of single-cell sequencing data. CAPN8, IRX2, and SPINK13 may serve as novel targets of targeted and immune-based therapies in lung adenocarcinoma.

Die IgG4-assoziierte Erkrankung ist eine immunvermittelte chronische, systemische und autoinflammatorische Erkrankung, die verschiedene Organe im gesamten Körper betreffen kann. Am häufigsten sind die Bauchspeicheldrüse und die Gallenwege betroffen. Aufgrund der vielfältigen klinischen Erscheinungsformen der Krankheit sind viele Organe betroffen. Daher kann es leicht zu Fehldiagnosen kommen oder sie kann übersehen werden. Der Verdauungstrakt ist ein selten betroffenes System, und die meisten IgG4-assoziierten Magenerkrankungen werden mittels Endoskopie als Tumoren diagnostiziert. In diesem Artikel wird über zwei spezielle Fälle von IgG4-assoziierten Erkrankungen mit atrophischer Gastritis und Darmpolypen berichtet, um eine empirischere und theoretische Grundlage für die klinische Diagnose und Therapie zu schaffen.

A photoredox/nickel-catalyzed selective 1,4-arylsulfonation of 1,3-enynes to access structurally diverse sulfone-containing allenes has been established with low catalyst loading.