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In this study, tungsten oxide films were fabricated on ITO-coated glass substrates using DC reactive magnetron sputtering with varying argon to oxygen ratios. The influence of these ratios on the microstructure and electrochromic properties of the resulting WO3 films were examined. The microstructure was characterized using X-ray diffraction, scanning electron microscopy, and energy dispersive spectroscopy, which allowed for the determination of the percentage of atoms in the film. The surface morphology and roughness were measured using atomic force microscopy, while the film thickness was determined using a profilometer. The electrochromic properties of the tungsten oxide films were evaluated using a combination of ultraviolet-visible spectrophotometer and electrochemical workstation. The findings suggest that the electrochromic properties of the tungsten oxide films can be effectively tuned by manipulating the argon to oxygen ratio. Specifically, the tungsten oxide films exhibited optimal electrochromic performance when sputtered with an argon to oxygen ratio of 50 sccm:10 sccm (flux ratio). This resulted in a large optical modulation amplitude (ΔT = 56.97%), fast switching speed (tc = 5.8 s, tb = 3.4 s), high coloring efficiency (CE = 52.5 cm2/C), and stable ion storage capacity. These results highlight the potential of magnetron sputtering engineering techniques in the development of high-performance electrochromic films.

The DArk Matter Particle Explorer (DAMPE) is well suitable for searching for monochromatic and sharp $\gamma$-ray structures in the GeV$-$TeV range thanks to its unprecedented high energy resolution. In this work, we search for $\gamma$-ray line structures using five years of DAMPE data. To improve the sensitivity, we develop two types of dedicated data sets (including the BgoOnly data which is the first time to be used in the data analysis for the calorimeter-based gamma-ray observatories) and adopt the signal-to-noise ratio optimized regions of interest (ROIs) for different DM density profiles. No line signals or candidates are found between 10 and 300 GeV in the Galaxy. The constraints on the velocity-averaged cross section for $\chi\chi \to \gamma\gamma$ and the decay lifetime for $\chi \to \gamma\nu$, both at 95% confidence level, have been calculated and the systematic uncertainties have been taken into account. Comparing to the previous Fermi-LAT results, though DAMPE has an acceptance smaller by a factor of $\sim 10$, similar constraints on the DM parameters are achieved and below 100 GeV the lower limits on the decay lifetime are even stronger by a factor of a few. Our results demonstrate the potential of high-energy-resolution observations on dark matter detection., Comment: 14 pages, 8 figures. Update the content to keep up with the published version

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg

Yue-Ling Peng,1 Yan Zhang,1 Lin Pang,2 Ya-Fang Dong,3 Mu-Ye Li,4 Hui Liao,5 Rong-Shan Li1 1Department of Nephrology, Shanxi Provincial People’s Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pathology and Pathophysiology, School of Basic Medicine, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Ocular Fundus Diseases, Shanxi Eye Hospital, Shanxi Medical University, Taiyuan, People’s Republic of China; 5Drug Clinical Trial Institution, Shanxi Provincial People’s Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, People’s Republic of ChinaCorrespondence: Rong-Shan Li, Department of Nephrology, Shanxi Provincial People’s Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, People’s Republic of China, Email rongshanli@126.comBackground: Increasing evidence suggests that immune modulation contributes to the pathogenesis and progression of diabetic nephropathy (DN). However, the role of immune modulation in DN has not been elucidated. The purpose of this study was to search for potential immune-related therapeutic targets and molecular mechanisms of DN.Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. A total of 1793 immune-related genes were acquired from the Immunology Database and Analysis Portal (ImmPort). Weighted gene co-expression network analysis (WGCNA) was performed for GSE142025, and the red and turquoise co-expression modules were found to be key for DN progression. We utilized four machine learning algorithms, namely, random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), and k-nearest neighbor (KNN), to evaluate the diagnostic value of hub genes. Immune infiltration patterns were analyzed using the CIBERSORT algorithm, and the correlation between immune cell type abundance and hub gene expression was also investigated.Results: A total of 77 immune-related genes of advanced DN were selected for subsequent analyzes. Functional enrichment analysis showed that the regulation of cytokine–cytokine receptor interactions and immune cell function play a corresponding role in the progression of DN. The final 10 hub genes were identified through multiple datasets. In addition, the expression levels of the identified hub genes were corroborated through a rat model. The RF model exhibited the highest AUC. CIBERSORT analysis and single-cell sequencing analysis revealed changes in immune infiltration patterns between control subjects and DN patients. Several potential drugs to reverse the altered hub genes were identified through the Drug-Gene Interaction database (DGIdb).Conclusion: This pioneering work provided a novel immunological perspective on the progression of DN, identifying key immune-related genes and potential drug targets, thus stimulating future mechanistic research and therapeutic target identification for DN.Keywords: diabetic nephropathy, machine learning, single cell, cell-to-cell communication, immune therapy

Ring gear is an important transmission component, but restricted by its ring-shape structure, the tooth surfaces are pretty hard to be finished after heat treatment. Honing is the most commonly used finishing technique for external gear, but for ring gear, it is inconvenient. In this paper, a new type of cone-shape honing wheel is proposed and the honing mechanism is studied for improving the honing performance of ring gear. First of all, the mathematical model of the honing technology by use of cone-shape honing wheel is built, and the merits of the new honing method are discussed. Then, the contact conditions between the honing wheel and the work gear are analyzed, and it is found that the tool tilt angle of the honing wheel has good influences on the honing mark distribution of the work gear. Finally, the honing simulations for ring gear by use of cone-shape honing wheel are carried out, by which the feasibility of the new honing technique are verified.

Background Mycoheterotrophs, acquiring organic carbon and other nutrients from mycorrhizal fungi, have evolved repeatedly with substantial plastid genome (plastome) variations. To date, the fine-scale evolution of mycoheterotrophic plastomes at the intraspecific level is not well-characterized. A few studies have revealed unexpected plastome divergence among species complex members, possibly driven by various biotic/abiotic factors. To illustrate evolutionary mechanisms underlying such divergence, we analyzed plastome features and molecular evolution of 15 plastomes of Neottia listeroides complex from different forest habitats. Results These 15 samples of Neottia listeroides complex split into three clades according to their habitats approximately 6 million years ago: Pine Clade, including ten samples from pine-broadleaf mixed forests, Fir Clade, including four samples from alpine fir forests and Fir-willow Clade with one sample. Compared with those of Pine Clade members, plastomes of Fir Clade members show smaller size and higher substitution rates. Plastome size, substitution rates, loss and retention of plastid-encoded genes are clade-specific. We propose to recognized six species in N. listeroides complex and slightly modify the path of plastome degradation. Conclusions Our results provide insight into the evolutionary dynamics and discrepancy of closely related mycoheterotrophic orchid lineages at a high phylogenetic resolution.

PurposeInvestigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes.MethodsPatients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs.ResultsIn comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs.ConclusionThe present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.

GRB 221009A is the brightest gamma-ray burst ever detected since the discovery of this kind of energetic explosions. However, an accurate measurement of the prompt emission properties of this burst is very challenging due to its exceptional brightness. With joint observations of \textit{Insight}-HXMT and GECAM-C, we made an unprecedentedly accurate measurement of the emission during the first $\sim$1800 s of GRB 221009A, including its precursor, main emission (ME, which dominates the burst in flux), flaring emission and early afterglow, in the hard X-ray to soft gamma-ray band from $\sim$ 10 keV to $\sim$ 6 MeV. Based on the GECAM-C unsaturated data of the ME, we measure a record-breaking isotropic equivalent energy ($E_{\rm iso}$) of $\bf \sim 1.5 \times 10^{55}$ erg, which is about eight times the total rest-mass energy of the Sun. The early afterglow data require a significant jet break between 650 s and 1100 s, most likely at $\sim950$ s from the afterglow starting time $T_{AG}$, which corresponds to a jet opening angle of $\sim {0.7^\circ} \ (\eta_\gamma n)^{1/8}$, where $n$ is the ambient medium density in units of $\rm cm^{-3}$ and $\eta_\gamma$ is the ratio between $\gamma$-ray energy and afterglow kinetic energy. The beaming-corrected total $\gamma$-ray energy $E_{\gamma}$ is $\sim 1.15 \times10^{51} \ (\eta_\gamma n)^{1/4}$ erg, which is typical for long GRBs. These results suggest that this GRB may have a special central engine, which could launch and collimate a very narrowly beamed jet with an ordinary energy budget, leading to exceptionally luminous gamma-ray radiation per unit solid angle. Alternatively, more GRBs might have such a narrow and bright beam, which are missed by an unfavorable viewing angle or have been detected without distance measurement., Comment: Submitted to National Science Review. This paper is under press embargo, contact the corresponding author for details

The gamma-ray detectors (GRDs) of GECAM-C onborad SATech-01 satellite is designed to monitor gamma-ray transients all over the sky from 6 keV to 6 MeV. The energy response matrix is the key to do spectral measurements of bursts, which is usually generated from GEANT4 simulation and partially verified by the ground calibration. In this work, energy response matrix of GECAM-C GRD is cross-calibrated with Fermi/GBM and Swift/BAT using a sample of Gamma-Ray Bursts (GRBs) and Soft Gamma-Ray Repeaters (SGRs). The calibration results show there is a good agreement between GECAM-C and other reasonably well calibrated instrument (i.e. Fermi/GBM and Swift/BAT). We also find that different GRD detectors of GECAM-C also show consistency with each other. All these results indicate that GECAM-C GRD can provide reliable spectral measurements., preliminary version, will be updated soon

As a new member of GECAM mission, GECAM-C (also named High Energy Burst Searcher, HEBS) was launched onboard the SATech-01 satellite on July 27th, 2022, which is capable to monitor gamma-ray transients from $\sim$ 6 keV to 6 MeV. As the main detector, there are 12 gamma-ray detectors (GRDs) equipped for GECAM-C. In order to verify the GECAM-C GRD detector performance and to validate the Monte Carlo simulations of detector response, comprehensive on-ground calibration experiments have been performed using X-ray beam and radioactive sources, including Energy-Channel relation, energy resolution, detection efficiency, SiPM voltage-gain relation and the non-uniformity of positional response. In this paper, the detailed calibration campaigns and data analysis results for GECAM-C GRDs are presented, demonstrating the excellent performance of GECAM-C GRD detectors., third version

Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) is a dedicated mission, launched in December 2020, for gamma-ray transients, including gamma-ray bursts (GRBs) and soft gamma repeater (SGR) bursts in the multimessenger and multiwavelength astronomy era. Since GECAM consists of two independent spacecrafts (or say instruments), and the framework of data analysis for multiple spacecrafts is distinctive from that for only one spacecraft, which is the case for most GRB missions, we developed a dedicated pipeline called Energetic Transients Joint Analysis System for Multi-INstrument (ETJASMIN) for GECAM mission. This pipeline has been naturally extended to incorporate data from other gamma-ray instruments, including the operating missions, such as Insight-HXMT/HE, Fermi/GBM, Swift/BAT, INTEGRAL/SPI-ACS, Konus-Wind, and GRID, as well as the forthcoming missions, such as SVOM/GRM and HEBS. In this paper, we present this pipeline with a focus on the data analysis procedures, methodology, and results in terms of the localization, verification (classification), spectral, and temporal analyses of gamma-ray transients. We show that this pipeline could provide more accurate, reliable, and comprehensive results than that of individual spacecraft, which is beneficial for gamma-ray transients observation.

Summary Pine wilt disease (PWD), caused by the pine wood nematode, Bursaphelenchus xylophilus, is an international quarantine forest disease that damages pine forests over extensive areas and causes massive economic losses. To provide valuable guidelines on screening pesticides against B. xylophilus and the selection of common solvents, we investigated the effects of different concentrations of emamectin benzoate, matrine and four solvents (methanol, ethanol, acetone and dimethyl sulfoxide) on the mortality and locomotor behaviour of B. xylophilus. Emamectin abamectin has nematicidal activity and mitigates locomotor activity of B. xylophilus at a low concentration. The LC50 of emamectin benzoate was 0.0354 mg l−1 at 72 h. Bursaphelenchus xylophilus mortality following exposure to matrine was low; however, nematode locomotor activity decreased by 62.5% following exposure to 500 mg l−1 matrine for 8 h. Additionally, B. xylophilus locomotor activity decreased significantly following exposure to 5 and 10% methanol, ethanol, acetone and dimethyl sulfoxide (DMSO) when compared with that of the water control. Emamectin benzoate and matrine, and high concentrations of four solvents (methanol, ethanol, acetone, and DMSO) inhibit B. xylophilus movement, which, in turn, could affect nematode infectivity. Moreover, low concentrations of non-lethal doses of emamectin benzoate should be considered for application in the control of nematodes, with matrine being an environmentally friendly and potentially nematicidal agent.

ObjectivesThis study was performed to investigate the relationship between right ventricular free wall longitudinal strain (RVFWSL) and low cardiac output syndrome (LCOS) after surgical aortic valve replacement (SAVR) and to further explore its association with readmission within 2 years in patients who developed LCOS after SAVR.MethodsThis single-center retrospective observational study involved consecutive patients who underwent SAVR at our hospital from May 2018 to June 2020. Preoperative echocardiography was obtained within 3 days before SAVR. The longitudinal strain of the right ventricle was analyzed using the right ventricle as the main section, and the RVFWSL and right ventricular four-chamber longitudinal strain (RV4CSL) were obtained. The primary observation was the occurrence of LCOS. The secondary prognostic indicators were mainly the readmission rates within 2 years.ResultsIn total, 146 patients were finally included in this study. The RVFWSL was significantly lower in the LCOS group than in the No-LCOS group (16.63 ± 2.10) vs. (23.95 ± 6.33), respectively; P < 0.001). The multivariate regression analysis showed that the RVFWSL was associated with LCOS (odds ratio, 1.676; 95% confidence interval, 1.258–2.232; P < 0.001). The receiver operating characteristic curve showed that the cut-off value for RVFWSL to predict LCOS was less than –18.3, with an area under the curve of 0.879, sensitivity of 100%, and specificity of 80.47%. The multivariate regression analysis showed that LCOS was an independent risk factor for readmission within 2 years in patients undergoing SAVR.ConclusionPatients with RVFWSL (

Eight new species from China, Cheirostylis chuxiongensis, C. yei, Myrmechis lingulata, M. longii, Bulbophyllum ximaense, B. xizangense, B. retusum and B. pulcherissimum, are described and illustrated. Cheirostylis chuxiongensis differs from C. thailandica by having 5–9 irregular and papillae-like calli on each side in the sac of the lip, epichile with entire lobes, petals narrowly obliquely obovate and an apex that is not recurved. Cheirostylis yei is easily distinguished from its relatives similar by having a long stem, pubescent ovary and sepals, epichile lobes with irregular and undulate margins, a subquadrate callus without teeth in the saccate hypochile. Myrmechis lingulata differs from M. chinensis by having a simple and lanceolate to ligulate lip, glabrous bracts and ovary, oblique and narrowly ovate petals. Myrmechis longii differs from M. pumila by having white-veined leaves, oblong-lanceolate epichile lobes, and viscidium attached to the middle of the caudicle. Bulbophyllum ximaense is easily distinguished from its relatives similar by having distant pseudobulbs, shorter scape, an inflorescence with 9–16 orange-red flowers, shorter lateral sepals with a long acuminate apex, incurved and tubular apical margins, a papillate lip disk and triangular-subulate stelidia. Bulbophyllum xizangense is easily distinguished from its relatives similar by having narrow lanceolate leaves, shorter inflorescence with 1–3 greenish-yellow flowers, falcate-ovoid lateral sepals, a lip with small lateral lobes and 3 keels at the base. Bulbophyllum retusum differs from B. spathulatum by having shorter inflorescence, peduncles with 2 tubular sheaths, dorsal sepals with a retuse apex, lateral sepals with lower edges that are connate to each other and free and divergent toward the apex, obovate petals with an acute or slightly retuse apex. Bulbophyllum pulcherissimum differs from B. lopalanthum by its 5-veined dorsal sepal, ovate-lanceolate lateral sepals, obliquely ovate-oblong petal, erose-toothed margins and obovate lip with a large, oblong basal callus, and an obtuse base. In addition, three species (Bulbophyllum frostii, B. raskotii and B. nematocaulon) are reported for the first time in China.

Five new species (Gastrochilus yei, Gastrochilus minimus, Luisia simaoensis, Taeniophyllum xizangense, Tuberolabium subulatum) and two newly recorded species (Cleisostoma tricornutum, Luisia inconspicua) of Vandeae (Orchidaceae) from China are described and illustrated. Gastrochilus yei is similar to G. affinis and G. nepalensis, but differs from them by having an epichile not lobed, the apex of the hypochile not bilobed, and a tine on the apex of the leaf. Gastrochilus minimus is similar to G. acinacifolius, but can be distinguished from the latter by having a flabellate epichile that is densely hirsute on the adaxial surface and an inconspicuous central cushion; in addition, the hypochile of G. minimus has a keel that extends to the apex of the epichile. Taeniophyllum xizangense is similar to T. stella and T. radiatum, but it is distinguished from them by having much bigger flowers, inflorescences densely covered with short-bristly hairs, papillae on the external surface of sepals, and bigger triangular-ovate viscidium. Luisia simaoensis is similar to L. magniflora and L. ramosii, but can be easily distinguished from them by having lateral sepals longer than dorsal sepals and petals, lip with irregular and waved margins, and lip with bilobed apex. Luisia inconspicua is moved from Gastrochilus to Luisia based on phylogenetic analyses of plastid matK sequence data. Tuberolabium subulatum is similar to T. carnosum, but it can be easily distinguished from the latter by having an inflorescence much shorter than the leaves, yellow sepals and petals, and many small papillae outside the lip lobes., Highlights • Five new orchid species belonging to Vandeae were described based on morphological characters. • Two new recorded orchids of China were reported. • Phylogenetic position of Luisia inconspicua is confirmed based on molecular systematics.

Yi-Hui Liu,1 Yan Guo,2 Hong Xu,1 Hui Feng,1 Dong-Ya Chen1 1Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Third Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yi-Hui LiuDepartment of Digestive Hepatology, Hangzhou Red Cross Hospital, No. 208 of Huancheng East Road, Xiacheng District, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaTel +8613588227972Email yhl_123drsea@163.comObjective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.Keywords: non-alcoholic simple fatty liver disease, antituberculosis drugs, drug-induced liver injury

The Earth occultation technique has broad applications in both astronomy and atmospheric density measurements. We construct the background model during the occultation of the Crab Nebula observed by the Insight-Hard X-ray Modulation Telescope (Insight-HXMT) at energies between 6 keV and 100 keV. We propose a Bayesian atmospheric density retrieval method based on the Earth occultation technique, combining Poisson and Gaussian statistics. By modeling the atmospheric attenuation of X-ray photons during the occultation, we simultaneously retrieved the neutral densities of the atmosphere at different altitude ranges. Our method considers the correlation of densities between neighboring atmospheric layers and reduces the potential systematic bias to which previous work may be subject. Previous analyses based on light curve fitting or spectral fitting also lost some spectral or temporal information of the data. In contrast to previous work, the occultation data observed by the three telescopes onboard Insight-HXMT is fully used in our analysis, further reducing the statistical error in density retrieval. We apply our method to cross-check the (semi-)empirical atmospheric models, using 115 sets of occultation data of the Crab Nebula observed by Insight-HXMT. We find that the retrieved neutral density is ~10%, ~20%, and ~25% less than the values of the widely used atmospheric model NRLMSISE-00, in the altitude range of 55--80 km, 80--90 km, and 90--100 km, respectively. We also show that the newly released atmospheric model NRLMSIS 2.0 is generally consistent with our density measurements., 20 pages, 12 figures, accepted for publication in ApJS

Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD.

Cymbidium is an orchid genus that has undergone rapid radiation and has high ornamental, economic, ecological and cultural importance, but its classification based on morphology is controversial. The plastid genome (plastome), as an extension of plant standard DNA barcodes, has been widely used as a potential molecular marker for identifying recently diverged species or complicated plant groups. In this study, we newly generated 237 plastomes of 50 species (at least two individuals per species) by genome skimming, covering 71.4% of members of the genus Cymbidium. Sequence-based analyses (barcoding gaps and automatic barcode gap discovery) and tree-based analyses (maximum likelihood, Bayesian inference and multirate Poisson tree processes model) were conducted for species identification of Cymbidium. Our work provides a comprehensive DNA barcode reference library for Cymbidium species identification. The results show that compared with standard DNA barcodes (rbcL + matK) as well as the plastid trnH-psbA, the species identification rate of the plastome increased moderately from 58% to 68%. At the same time, we propose an optimized identification strategy for Cymbidium species. The plastome cannot completely resolve the species identification of Cymbidium, the main reasons being incomplete lineage sorting, artificial cultivation, natural hybridization and chloroplast capture. To further explore the potential use of nuclear data in identifying species, the Skmer method was adopted and the identification rate increased to 72%. It appears that nuclear genome data have a vital role in species identification and are expected to be used as next-generation nuclear barcodes.

Four new species of Orchidaceae from China, Heminium lijiangense, Peristylus fasciculatus, Platanthera milinensis, and Ponerorchis gongshanensis, together with a new country record, Peristylus tenuicallus, are described and illustrated based on morphological and/or phylogenetic analyses. Heminium lijiangense is closely related to H. elisabethae but differs from it by having the dorsal sepal ovate-orbicular and lip mid-lobe distinctly shorter than lateral lobes. P. fasciculatus is close to Peristylus tradescantifolius but is distinguished from it by having several fascicled and straight, root-like tubers (vs. one or two oblongoid tubers), old stems usually persistent, middle lobe of lip narrowly ligulate-lanceolate and half as long as the lateral lobes (vs. middle lobe deltoid, about a third as long as the lateral lobes or less), a raised callus at the base of each lateral lobe (vs. callus absent), spur gradually attenuate toward the apex (vs. spur clavate). Platanthera milinensis is similar to P. stenochila by sharing small green flowers and lip without a spur, but differs in having a creeping rhizome, a corymbose inflorescence, and a broadly ovate and slightly 3-lobed lip. Ponerochis gongshanensis is similar to P. faberi in its small flowers, but differs in having a linear leaf c. 3 mm wide (vs. leaf 5–13 mm wide), in the lip having collar-like raised margins on the sides of the spur entrance, and a mid-lobe which is notched at the apex but not divided into two divergent lobules that are nearly as large as the lateral lobes, as in P. faberi. All the proposed species obtained high support in phylogenetic analysis as new species. The recently described genus Apetalanthe is reduced to synonymy of Ponerorchis and a new combination is made., Highlights • Four new species of Orchidinae (Orchidaceae) are described and illustrated from China based on morphological and phylogenetic analyses. • The recently described genus Apetalanthe is reduced to synonymy of Ponerorchis. • Peristylus tenuicallus is described as new record of China.

ObjectiveThis study aims to investigate anxiety and its influencing factors in patients with drug-induced liver injury (DILI).Materials and MethodsNinety-four patients with DILI were enrolled and evaluated with a self-rating anxiety scale (SAS). According to the anxiety score, they were divided into four groups: the non-anxiety, mild anxiety, moderate anxiety, or severe anxiety groups, and the scores were analyzed based on demographic and biochemical indicators.ResultsOf the 94 patients with DILI, 63 did not have anxiety and 31 had anxiety (32.9%), of which 27 had mild, 3 had moderate, and 1 had severe anxiety. There were no statistically significant differences in gender, age, occupation, and level of education between the groups (F = 1.42, H = 2.361, H = 6.751, H = 1.796, and P > 0.05); anxiety score and degree of anxiety between the types of drugs that led to the liver injury (H = 0.812, H = 1.712, and P > 0.05); anxiety score between the different degrees of liver injury (H = 2.836, H = 4.957, P > 0.05); or length of hospital stay or prognosis between the degrees of anxiety (F = 1.487, H = 0.761, P > 0.05). However, there were statistically significant differences in the degree of anxiety between different degree and types of liver injury (H = 7.981, H = 8.208, P < 0.05).ConclusionPatients with DILI may have anxiety, especially mild anxiety. The occurrence of anxiety in patients with DILI is not related to gender, age, occupation, or level of education but may be related to the degree and type of liver injury. Anxiety has no impact on the length of stay in hospital or the prognosis of the DILI. These findings may contribute to the development of management strategies for patients with DILI.

PurposeLumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization.MethodsA total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01–0.08 Hz), the slow-4 band (0.027–0.073 Hz), and the slow-5 band (0.01–0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect.ResultsCompared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum_Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band.ConclusionThe present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH.

Objective To report the first case of adult late⁃onset propionic acidemia (PA) caused by PCCB gene mutation in China, and summary the clinical and molecular pathological characteristics of patients with late⁃onset propionic acidemia. Methods and Results The clinical manisfestions of an eighteen⁃year⁃old male patient were acute onset of symmetrical injury at bilateral basal ganglia which induced metabolic encephalopathy with involuntury movement. Tandem mass spectrometry (MS/MS) test results of dried blood spots indicated that propionyl carnitine (C3) was 10.37 μmol/L, and the ratio of propionyl carnitine to acetyl carnitine (C3/C2) was 0.69. Gas chromatography⁃mass spectrometry (GC/MS) test results indicated urine 3⁃hydroxypropionic acid was 18 μmol/L, methyl citrate level was 12.70 μmol/L. The gene results detected a homozygous pathogenic mutation (exon 10: c.1087T＞C, p.Ser363Pro) in the PCCB gene. His parents had a heterozygous mutation in PCCB gene exon 10 c.1087T＞C (p.Ser363Pro), which was consistent with the phenomenon of family co⁃segregation, and the mutation site was consistent with a suspected pathogenic variant. The final molecular pathological diagnosis was late⁃onset propionic acidemia. Following the protein restriction diet, high⁃dose L⁃carnitine injection, and ammonia⁃lowering treatment, the dried blood spots propionic acid level and the urine 3⁃hydroxypropionic acid level decreased significantly. Conclusions The mutation exon c.1087T＞C (p.Ser363Pro) is a rare and highly suspected pathogenic mutation of PCCB gene. MS/MS and GC/MS detection combined with whole exome sequencing technology is very important in the diagnosis of late⁃onset propionic acidemia. doi:10.3969/j.issn.1672⁃6731.2021.04.010

Liparis aureolabella and L. mengziensis, two new species from the karst region of southwestern China, and L. bingzhongluoensis, a new species from montane region in Yunnan, are described and illustrated. L. aureolabella is easily distinguished from its relatives by having abaxially purple leave with purple reticulate veins prominent adaxially, a lip auriculate at base, and falcate-lanceolate pollinia. Liparis mengziensis is closely related to L. petiolata and L. auriculata, but differs from them by having an ovate to broadly ovate leaf, purple lip and apex connate along the margins. Liparis bingzhongluoensis is similar to Liparis nanlingensis, but the new species is characterized by having a lip with two transparent ridges on its disc, longitudinally concave basal callus and triangular column wings. Phylogenetic analyses based on nuclear ribosomal ITS and plastid matK sequences showed that L. aureolabella and L. mengziensis are nested with L. petiolata or L. auriculata in a monophyletic clade. L. bingzhongluoensis is sister to a clade formed by L. nanlingensis, L. tsii, L. sasakii and L. krameri. Moreover, morphological comparisons strongly support that the three species as separated species newly to science.

Stress-induced depression is common worldwide. NAc, a “reward” center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. In this study, we induced depression-like behaviors with CSDS and chronic mild stress in male mice to mimic social and environmental factors, respectively, and observed animal behaviors with social interaction test, tail suspension test, and sucrose preference test. To determine the role of neuronal nitric oxide synthase (nNOS) and its product nitric oxide (NO), we used brain region-specifically nNOS overexpression and stereotaxic injection of NO inhibitor or donor. Moreover, the downstream molecular cyclin-dependent kinase 5 (CDK5) was explored by conditional KO and gene mutation. We demonstrate that nNOS-implicated mechanisms in NAc shell (NAcSh), including increased cell number, increased protein expression levels, and increased specific enzyme activity, contribute the susceptibility to social defeat and the following depression-like behaviors. NAcSh nNOS does not directly respond to chronic mild stress but facilitates the depression-like behaviors. The increased NAcSh nNOS expression after CSDS leads to the social avoidance and depression-like behaviors in defeated mice, which is dependent on the nNOS enzyme activity and NO production. Moreover, we identify the downstream signal in NAcSh. S-nitrosylation of CDK5 by NO contributes to enhanced CDK5 activity, leading to depression-related behaviors in susceptible mice. Therefore, NAcSh nNOS mediates susceptibility to social defeat stress and the depression-like behaviors through CDK5.SIGNIFICANCE STATEMENTStress-induced depression is common worldwide, and chronic exposure to social and psychological stressors is important cause of human depression. Our study conducted with chronic social defeat stress mice models demonstrates that nNOS in NAcSh is crucial to regulate the susceptibility to social defeat stress and the following depression-like behaviors, indicating NAcSh nNOS as the responding molecule to social factors of depression. Moreover, we discover the downstream mechanism of NAcSh nNOS in mediating the susceptibility is NO and S-nitrosylation of CDK5. Thus, NAcSh nNOS mediates susceptibility to social defeat stress through CDK5 is a potential mechanism for depression, which may interpret how the brain transduces social stress exposure into depression.

Overactivation of N-methyl-D-aspartate receptor (NMDAR) in the spinal cord dorsal horn (SDH) in the setting of injury represents a key mechanism of neuropathic pain. However, directly blocking NMDAR or its downstream signaling, interaction between postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS), causes analgesic tolerance, mainly due to GABAergic disinhibition. The aim of this study is to explore the possibility of preventing analgesic tolerance through co-targeting NMDAR downstream signaling and γ-aminobutyric acid type A receptors (GABAARs). Methods: Mechanical/thermal hyperalgesia were quantified to assess analgesic effects. Miniature postsynaptic currents were tested by patch-clamp recording to evaluate synaptic transmission in the SDH. GABA-evoked currents were tested on HEK293 cells expressing different subtypes of recombinant GABAARs to assess the selectivity of (+)-borneol and ZL006-05. The expression of α2 and α3 subunits of GABAARs and BDNF, and nNOS-PSD-95 complex levels were analyzed by western blotting and coimmunoprecipitation respectively. Open field test, rotarod test and Morris water maze task were conducted to evaluate the side-effect of ZL006-05. Results: (+)-Borneol selectively potentiated α2- and α3-containing GABAARs and prevented the disinhibition of laminae I excitatory neurons in the SDH and analgesic tolerance caused by chronic use of ZL006, a nNOS-PSD-95 blocker. A dual-target compound ZL006-05 produced by linking ZL006 and (+)-borneol through an ester bond blocked nNOS-PSD-95 interaction and potentiated α2-containing GABAAR selectively. Chronic use of ZL006-05 did not produce analgesic tolerance and unwanted side effects. Conclusion: By targeting nNOS-PSD-95 interaction and α2-containing GABAAR simultaneously, chronic use of ZL006-05 can avoid analgesic tolerance and unwanted side effects. Therefore, we offer a novel candidate drug without analgesic tolerance for treating neuropathic pain.

Rationale: Stroke is a leading cause of adult disability worldwide, but no drug provides functional recovery during the repair phase. Accumulating evidence demonstrates that environmental enrichment (EE) promotes stroke recovery by enhancing network excitability. However, the complexities of utilizing EE in a clinical setting limit its translation. Methods: We used multifaceted approaches combining electrophysiology, chemogenetics, optogenetics, and floxed mice in a mouse photothrombotic stroke model to reveal the key target of EE-mediated stroke recovery. Results: EE reduced tonic gamma-aminobutyric acid (GABA) inhibition and facilitated phasic GABA inhibition in the peri-infarct cortex, thereby promoting network excitability and stroke recovery. These beneficial effects depended on GAT-1, a GABA transporter regulating both tonic and phasic GABA signaling, as EE positively regulated GAT-1 expression, trafficking, and function. Furthermore, GAT-1 was necessary for EE-induced network plasticity, including structural neuroplasticity, input synaptic strengthening in the peri-infarct cortex, output synaptic strengthening in the corticospinal tract, and sprouting of uninjured corticospinal axons across the midline into the territory of denervated spinal cord, and functional recovery from stroke. Moreover, restoration of GAT-1 function in the peri-infarct cortex by its overexpression showed similar beneficial effects on stroke recovery as EE exposure. Conclusion: GAT-1 is a key molecular substrate of the effects of EE on network excitability and consequent stroke recovery and can serve as a novel therapeutic target for stroke treatment during the repair phase.

Posttraumatic stress disorder subjects usually show impaired recall of extinction memory, leading to extinguished fear relapses. However, little is known about the neural mechanisms underlying the impaired recall of extinction memory. We show here that the activity of dorsal hippocampus (dHPC) to infralimbic (IL) cortex circuit is essential for the recall of fear extinction memory in male mice. There were functional neural projections from the dHPC to IL. Using optogenetic manipulations, we observed that silencing the activity of dHPC-IL circuit inhibited recall of extinction memory while stimulating the activity of dHPC-IL circuit facilitated recall of extinction memory. “Impairment of extinction consolidation caused by” conditional deletion of extracellular signal-regulated kinase 2 (ERK2) in the IL prevented the dHPC-IL circuit-mediated recall of extinction memory. Moreover, silencing the dHPC-IL circuit abolished the effect of intra-IL microinjection of ERK enhancer on the recall of extinction memory. Together, we identify a dHPC to IL circuit that mediates the recall of extinction memory, and our data suggest that the dysfunction of dHPC-IL circuit and/or impaired extinction consolidation may contribute to extinguished fear relapses.

The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00603-6) contains supplementary material, which is available to authorized users.

The metabolic syndrome (MetS) is a cluster of risk factors for cognitive impairment. We aimed to investigate the association between MetS and risk of persistent cognitive impairment in patients with a transient ischemic attack (TIA) or mild ischemic stroke. This is a prospective and observational study in consecutive patients with first-ever TIA or mild stroke (National Institutes of Health Stroke Scale score ≤ 6). Patients underwent Montreal cognitive assessment (MoCA) at hospital admission and day 30 after discharge. We defined cognitive impairment as a MoCA score of ≤26. Persistent cognitive impairment was defined as baseline cognitive impairment and an increase of

Background and purpose Anxiety disorder is a common mental health disorder. However, there are few safe and fast-acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal NOS (nNOS) with its carboxy-terminal PDZ ligand (CAPON) is involved in regulating anxiety-related behaviours. Here, we further investigated the anxiolytic effects of nNOS-CAPON disruptors in chronic stress-induced anxiety in animals. Experimental approach Mice were intravenously treated with nNOS-CAPON disruptors, ZLc-002 or Tat-CAPON12C, at the last week of chronic mild stress (CMS) exposure. We also infused corticosterone (CORT) into the hippocampus of mice to model anxiety behaviours and also delivered ZLc-002 or Tat-CAPON12C on the last week of chronic CORT treatment via pre-implanted cannula. Anxiety-related behaviours were examined using elevated plus maze, open field, novelty-suppressed feeding and light-dark (LD) tests. The level of nNOS-CAPON interaction was determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). The neural mechanisms underlying the behavioural effects of nNOS-CAPON uncoupling in anxiety animal models were assessed by western blot, immunofluorescence and Golgi-Cox staining. Key results ZLc-002 and Tat-CAPON12C reversed CMS- or CORT-induced anxiety-related behaviours. ZLc-002 and Tat-CAPON12C increased synaptogenesis along with improved dendritic remodelling in CMS mice or CORT-treated cultured neurons. Meanwhile, blocking nNOS-CAPON interaction significantly activated the cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) pathway, which is associated with synaptic plasticity. Conclusion and implications Collectively, these results provide evidence for the anxiolytic effects of nNOS-CAPON uncouplers and their underlying mechanisms in anxiety disorders.

Background. Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism. Methods. SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria. Results. Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ± 30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ± 46.8 vs. 421.7 ± 48.3 pg/ml; amylase: 2102.3 ± 165.3 vs. 3186.4 ± 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ± 50.3 vs. 332.4 ± 25.1 Hz; discharge amplitude: 33.4 ± 5.3 vs. 20.5 ± 2.9 μV). Conclusions. Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus- and α7nAChR-dependent mechanisms.

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons., Chronic pain usually induces anxiety. Here, the authors report that vmPFC nNOS-expressing neurons are activated by excitatory inputs from pPVT during chronic pain and subsequently induce anxiety-like behaviors in mice through promoting AMPAR trafficking.

About 5 per cent of follicular lymphoma (FL) cases are double‐hit (DH) lymphomas. Double‐hit follicular lymphoma (DHFL) cell lines can improve our understanding and drug development on FL. But there are only few DHFL cell lines. Here, we established a new MYC/BCL2 DHFL cell line, FL‐SJC. The cells were obtained from the hydrothorax of a patient with MYC/BCL2 DHFL and cultured for 140 passages in vitro. FL‐SJC cells demonstrated CD19++, CD20+, CD22++, HLA‐DR+, CD10+, CD38+, Lambda+ CD23‐, CD5‐ and Kappa‐. The chromosome karyotypic analysis confirmed the co‐existence of t(8;22)(q24;q11) and t(14;18)(q32;q21), as well as additional abnormalities involving chromosomes 2 and 3. Fluorescence in situ hybridization analysis (FISH) showed IGH/BCL2 fusion gene and the MYC rearrangement. In addition, the FL‐SJC cells displayed KMT2D/MLL2 and CREBBP gene mutations. After subcutaneous inoculation of FL‐SJC cells, the SCID mice developed solid tumour masses within 6‐8 weeks. FL‐SJC cells were proven to be free of Epstein‐Barr (EB) virus infection and be multidrug‐resistant. In a conclusion, the FL‐SJC cell line has been identified as a novel MYC/BCL2 double‐hit follicular lymphoma that can be used as a potentially available tool for the clinical and basic research, together with the drug development for MYC/BCL2 DHFL.

Purpose Tranexamic acid (TXA) has been widely used in hip and knee arthroplasty to reduce perioperative blood loss and blood transfusion, but the dosage and efficacy of TXA in posterior lumbar spinal surgery are not fully clear. The aim of this study was to investigate the efficacy and safety of TXA and to determine whether 2 doses of TXA could reduce the blood loss in primary single-segment or double-segment posterior lumbar fusion surgery. Materials and methods A total of 150 patients with lumbar degenerative disease undergoing posterior lumbar interbody fusion surgery between October 2017 and February 2019 were randomized to 3 groups. Group A was treated with 0.9% normal saline solution without TXA, group B was treated with a 15 mg/kg loading dose intravenous infusion 30 minutes before surgery, and group C was treated with a 15 mg/kg loading dose intravenous infusion 30 minutes before surgery; then, the same dose was administered again 3 hours later. The assessed outcomes were the operation time, the total blood loss, the hidden blood loss, postoperative drainage, blood transfusions, incidence of venous thromboembolism, and incision infection. Results The total blood loss, the hidden blood loss, and postoperative drainage were the lowest in group C. The amount of intraoperative blood loss was similar among the 3 groups. The hemoglobin and hematocrit values of the third postoperative day were the highest in group C. No significant differences in the incidence of complications and adverse events from TXA use were observed among the 3 groups. The use of TXA, the operation time, and the number of fusion segments were identified as risk factors related to total blood loss. Conclusion Two doses of TXA significantly reduced the total blood loss, the hidden blood loss and postoperative drainage, and decreased hemoglobin and hematocrit drop in patients undergoing posterior lumbar fusion without increasing the risk of complications.

Hai-Sheng You,1,* Chun-Xia Gao,1,* Hai-Bin Wang,2 Sai-Sai Luo,1 Si-Ying Chen,1 Ya-Lin Dong,1 Jun Lyu,3 Tao Tian4 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Hangzhou Cognitive N&T. Co., Ltd, Hangzhou, Zhengjiang, People’s Republic of China; 3Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao TianDepartment of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86-13572206784Fax +86-29-85324086Email tiantao0607@163.comJun LyuClinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi 710061, People’s Republic of ChinaTel +86 29 8532 3614Fax +86 29 8532 3473Email lujun2006@xjtu.edu.cnObjective: The disease complexity of metastatic non-small-cell lung cancer (mNSCLC) makes it difficult for physicians to make clinical decisions efficiently and accurately. The Watson for Oncology (WFO) system of artificial intelligence might help physicians by providing fast and precise treatment regimens. This study measured the concordance of the medical treatment regimens of the WFO system and actual clinical regimens, with the aim of determining the suitability of WFO recommendations for Chinese patients with mNSCLC.Methods: Retrospective data of mNSCLC patients were input to the WFO, which generated a treatment regimen (WFO regimen). The actual regimen was made by physicians in a medical team for patients (medical-team regimen). The factors influencing the consistency of the two treatment options were analyzed by univariate and multivariate analyses.Results: The concordance rate was 85.16% between the WFO and medical-team regimens for mNSCLC patients. Logistic regression showed that the concordance differed significantly for various pathological types and gene mutations in two treatment regimens. Patients with adenocarcinoma had a lower rate of “recommended” regimen than those with squamous cell carcinoma. There was a statistically significant difference in EGFR-mutant patients for “not recommended” regimens with inconsistency rate of 18.75%. In conclusion, the WFO regimen has 85.16% consistency rate with medical-team regimen in our treatment center. The different pathological type and different gene mutation markedly influenced the agreement rate of the two treatment regimens.Conclusion: WFO recommendations have high applicability to mNSCLC patients in our hospital. This study demonstrates that the valuable WFO system may assist the doctors better to determine the accurate and effective treatment regimens for mNSCLC patients in the Chinese medical setting.Keywords: metastatic non-small-cell lung cancer, Watson for Oncology, concordance, artificial intelligence, treatment recommendations

Additional file 1. Supplemental methods, tables, and figures.