A tissue-like neurotransmitter sensor for the brain and gut.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

Quantifying inactive lithium in lithium metal batteries.

Lithium metal anodes offer high theoretical capacities (3,860 milliampere-hours per gram)1, but rechargeable batteries built with such anodes suffer from dendrite growth and low Coulombic efficiency (the ratio of charge output to charge input), preventing their commercial adoption2,3. The formation of inactive ('dead') lithium- which consists of both (electro)chemically formed Li+ compounds in the solid electrolyte interphase and electrically isolated unreacted metallic Li0 (refs 4,5)-causes capacity loss and safety hazards. Quantitatively distinguishing between Li+ in components of the solid electrolyte interphase and unreacted metallic Li0 has not been possible, owing to the lack of effective diagnostic tools. Optical microscopy6, in situ environmental transmission electron microscopy7,8, X-ray microtomography9 and magnetic resonance imaging10 provide a morphological perspective with little chemical information. Nuclear magnetic resonance11, X-ray photoelectron spectroscopy12 and cryogenic transmission electron microscopy13,14 can distinguish between Li+ in the solid electrolyte interphase and metallic Li0, but their detection ranges are limited to surfaces or local regions. Here we establish the analytical method of titration gas chromatography to quantify the contribution of unreacted metallic Li0 to the total amount of inactive lithium. We identify the unreacted metallic Li0, not the (electro)chemically formed Li+ in the solid electrolyte interphase, as the dominant source of inactive lithium and capacity loss. By coupling the unreacted metallic Li0 content to observations of its local microstructure and nanostructure by cryogenic electron microscopy (both scanning and transmission), we also establish the formation mechanism of inactive lithium in different types of electrolytes and determine the underlying cause of low Coulombic efficiency in plating and stripping (the charge and discharge processes, respectively, in a full cell) of lithium metal anodes. We propose strategies for making lithium plating and stripping more efficient so that lithium metal anodes can be used for next-generation high-energy batteries.

Nontrivial phase matching in helielectric polarization helices: Universal phase matching theory, validation, and electric switching.

Second-order optical nonlinearity is the essential concept for realizing modern technologies of optical wavelength conversion. The emerging helical polarization fluid, dubbed helielectric nematic, now makes it possible to design and easily fabricate various polarization structures and control their optical responses. The matter family is demonstrated as an ideal liquid platform for nonlinear optical conversion and amplification with electric-reconfigurable tunability. We here develop a universal phase matching theory and reveal a nonclassic chirality-sensitive phase-matching condition in the polarization helices through both the numerical calculation and the experimental validations. The nonlinear optical amplification can be dramatically modulated with a contrast ratio of >100:1 by an in-plane electric field. Furthermore, we employ the director relaxation under electric fields coupled with nonlinear optical simulation to clarify the topology-light interactions.

Shape Anisotropy-Governed High-Performance Nanomagnetosol for In Vivo Magnetic Particle Imaging of Lungs.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has shown extensive lung manifestations in vulnerable individuals, putting lung imaging and monitoring at the forefront of early detection and treatment. Magnetic particle imaging (MPI) is an imaging modality, which can bring excellent contrast, sensitivity, and signal-to-noise ratios to lung imaging for the development of new theranostic approaches for respiratory diseases. Advances in MPI tracers would offer additional improvements and increase the potential for clinical translation of MPI. Here, a high-performance nanotracer based on shape anisotropy of magnetic nanoparticles is developed and its use in MPI imaging of the lung is demonstrated. Shape anisotropy proves to be a critical parameter for increasing signal intensity and resolution and exceeding those properties of conventional spherical nanoparticles. The 0D nanoparticles exhibit a 2-fold increase, while the 1D nanorods have a > 5-fold increase in signal intensity when compared to VivoTrax. Newly designed 1D nanorods displayed high signal intensities and excellent resolution in lung images. A spatiotemporal lung imaging study in mice revealed that this tracer offers new opportunities for monitoring disease and guiding intervention.

Effects of Bifidobacterium breve 207-1 on regulating lifestyle behaviors and mental wellness in healthy adults based on the microbiome-gut-brain axis: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Our study aimed to explore the efficacy of Bifidobacterium breve 207-1 on specific neurotransmitters and hormones and the ability to regulate lifestyle behaviors in healthy adults. METHODS: In total, 120 healthy adults with high mental stress, overweight, insomnia, and constipation were randomly assigned to receive low-dose B. breve 207-1 (LD, n = 40), high-dose B. breve 207-1 (HD, n = 40), or placebo (n = 40) for 28 days. Fecal and blood samples were collected and questionnaires were answered before and after the trial. Neurotransmitters and serum hormones were detected using enzyme-linked immunosorbent assay. The gut microbiota composition was assessed using 16 S rRNA sequencing. Short-chain fatty acids (SCFAs) concentrations were determined via gas chromatography-mass spectrometry (GC-MS). RESULTS: The primary outcome of our study was changes in mental wellness, including neurotransmitters, the hypothalamic-pituitary-adrena (HPA) axis hormones, and the psychological scales. The results showed that γ-aminobutyric acid (GABA) increased significantly and the HPA axis hormones were suppressed overall in the probiotic groups while 5-hydroxytryptamine (5-HT) did not change significantly. However, there was no significant change in mood scale scores. The secondary outcome focused on the ability of 207-1 to regulate the body and lifestyle of healthy adults (e.g., sleep, diet, exercise, etc.). The PSQI scores in the probiotics groups significantly decreased, indicating improved sleep quality. Meanwhile, the probiotic groups had a slight increase in exercise consumption while dietary intake stabilized. By physical examination, the participants showed weight loss although no statistically significant difference was observed between the groups. Then, validated by gut microbiota, changes in the gut microbiota were observed under the effective intervention of 207-1 while short-chain fatty acids (SCFAs) increased in the LD group, particularly acetic and propionic acids. There was a slight decrease in alpha-diversity in the HD group. CONCLUSION: Bifidobacterium breve 207-1 entered the organism and affected neurotransmitter and the HPA axis hormone levels via the microbiome-gut-brain axis. Meanwhile, 207-1 supplementation improved daily lifestyle behaviors in healthy adults, which may in turn lead to changes in their bodies (e.g. weight and lipid metabolism). However, this study did not find significant mood-modulating efficacy. The mechanism of the overall study is unclear, but we hypothesize that SCFAs may be the key pathway, and more experiments are needed for validation in the future. TRIAL REGISTRATION: This trial was retrospectively registered in the Chinese Clinical Trial Registry under the accession number ChiCTR2300069453 on March 16, 2023.

Spontaneous helielectric nematic liquid crystals: Electric analog to helimagnets.

Recently, a type of ferroelectric nematic fluid has been discovered in liquid crystals in which the molecular polar nature at molecule level is amplified to macroscopic scales through a ferroelectric packing of rod-shaped molecules. Here, we report on the experimental proof of a polar chiral liquid matter state, dubbed helielectric nematic, stabilized by the local polar ordering coupled to the chiral helicity. This helielectric structure carries the polar vector rotating helically, analogous to the magnetic counterpart of helimagnet. The helielectric state can be retained down to room temperature and demonstrates gigantic dielectric and nonlinear optical responses. This matter state opens a new chapter for developing the diverse polar liquid crystal devices.

[Relationship between gut microbiome and neurodevelopment in early life].

OBJECTIVE: To compare the differences in gut microbiome composition between children with good neurodevelopment and those with delayed neurodevelopment, and to analyze the relationship between gut microbiome and the neurodevelopment status of infants in early life. METHODS: The mothers were included at the Second West China Hospital from November 2020 to April 2021. Their infant stools were collected on day 0 and day 90 after birth, and the follow-up questionnaires at the corresponding time points were completed. Additionally, the Ages and Stages Questionnaires-Third Edition(ASQ-3) were completed by mothers at 12 months of age. The structure and diversity of gut microbiota were examined by 16S rRNA sequencing, and the relationship between gut microbiome and ASQ-3 questionnaire scores in early life was analyzed. RESULTS: According to the ASQ-3 scores, mothers and infants into neurodevelopment good group(G group, n=18) and neurodevelopmental delay group(D group, n=10). Compared with the D group, the relative abundance of the Firmicutes was significantly higher in the G group at day 0(P<0.05), while the level of the Proteobacteria was lower(P<0.05). At day 90 after birth, the relative abundance of the Actinobacteria, Bifidobacteriaceae and Enterococcaceae was significantly higher in the G group(P<0.05). In addition, alpha diversity was not statistically different between the two groups. Spearman's correlation analysis showed that Clostridiaceae of the postnatal day 0 infants was positively correlated with the communication domain score, but negatively associated with gross motor domain score in children at 12 months of age, whereas the relative abundance of Proteobacteria and Enterobacteriaceae of children at postnatal day 90 was negatively associated with communication development, while the relative abundance of Erysipelatoclostridiaceae showed a negative correlation with gross motor domain scores. CONCLUSION: The structure of the gut microbiome in early life between neurodevelopment good and delayed infants, and were associated with the development of communication and gross motor domain in infants at 12 months of age, suggesting that gut microbiome in early life may be related to the level of neurodevelopment in infants.

Adjuvant Chemotherapy for Patients with Adenocarcinoma of the Esophagogastric Junction: A Retrospective, Multicenter, Observational Study.

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.

Inhibition of hyaluronic acid degradation pathway suppresses glioma progression by inducing apoptosis and cell cycle arrest.

BACKGROUND: Abnormal hyaluronic acid (HA) metabolism is a major factor in tumor progression, and the metabolic regulation of HA mainly includes HA biosynthesis and catabolism. In glioma, abnormal HA biosynthesis is intimately involved in glioma malignant biological properties and the formation of immunosuppressive microenvironment; however, the role of abnormal HA catabolism in glioma remains unclear. METHODS: HA catabolism is dependent on hyaluronidase. In TCGA and GEPIA databases, we found that among the 6 human hyaluronidases (HYAL1, HYAL2, HYAL3, HYAL4, HYALP1, SPAM1), only HYAL2 expression was highest in glioma. Next, TCGA and CGGA database were further used to explore the correlation of HYAL2 expression with glioma prognosis. Then, the mRNA expression and protein level of HYAL2 was determined by qRT-PCR, Western blot and Immunohistochemical staining in glioma cells and glioma tissues, respectively. The MTT, EdU and Colony formation assay were used to measure the effect of HYAL2 knockdown on glioma. The GSEA enrichment analysis was performed to explore the potential pathway regulated by HYAL2 in glioma, in addition, the HYAL2-regulated signaling pathways were detected by flow cytometry and Western blot. Finally, small molecule compounds targeting HYAL2 in glioma were screened by Cmap analysis. RESULTS: In the present study, we confirmed that Hyaluronidase 2 (HYAL2) is abnormally overexpressed in glioma. Moreover, we found that HYAL2 overexpression is associated with multiple glioma clinical traits and acts as a key indicator for glioma prognosis. Targeting HYAL2 could inhibit glioma progression by inducing glioma cell apoptosis and cell cycle arrest. CONCLUSION: Collectively, these observations suggest that HYAL2 overexpression could promote glioma progression. Thus, treatments that disrupt HA catabolism by altering HYAL2 expression may serve as effective strategies for glioma treatment.

Breastfeeding might partially contribute to gut microbiota construction and stabilization of propionate metabolism in cesarean-section infants.

PURPOSE: This study was aimed to determine how delivery mode and feeding pattern influence the infant's gut microbiota construction and the variation of fecal microbial metabolites from a birth cohort. METHODS: Fecal samples collected from 61 full-term born Chinese infants at four time points: day 0, day 7, month 1, and month 3. Based on delivery mode (vaginal delivery [V] or cesarean section [C]) and feeding pattern (breastfeeding [B] or mixed feeding [M]), infants were divided into four groups, namely VB, CB, VM, and CM groups. The gut microbiota composition and bacterial diversity were assessed using 16S rRNA sequencing. Short-chain fatty acid (SCFA) concentrations were determined via gas chromatography-mass spectrometry (GC-MS). RESULTS: The CM group had a significantly higher relative abundance of Firmicutes (day 0 and month 1), Enterococcaceae (month 3), and Enterococcus (month 3) than the VB group and a significantly higher abundance of Firmicutes (month 1) and Blautia (month 3) than the CB group. The VB and CB groups exhibited a stable SCFA variation and a significantly lower level of propionate compared with the VM and CM groups. All groups showed an intense transition of enterotypes within 1 month and became stable at 3 months. The correlation between SCFA and enterotypes showed a significant positive correlation between Bifidobacteriaceae and acetate in the CB group (day 7 and month 3) and a significant positive correlation between Clostridiaceae and butyrate in the CB and VB groups (day 7 and month 3), respectively. CONCLUSION: These results indicated that C-section was associated with higher abundance of the phylum Firmicutes and family Enterococcaceae, and intense fluctuation of SCFA, at least propionate. And breastfeeding might partially contribute to gut microbiota construction and stabilization propionate metabolism in cesarean-section infants.

Intrinsically stretchable electrode array enabled in vivo electrophysiological mapping of atrial fibrillation at cellular resolution.

Electrophysiological mapping of chronic atrial fibrillation (AF) at high throughput and high resolution is critical for understanding its underlying mechanism and guiding definitive treatment such as cardiac ablation, but current electrophysiological tools are limited by either low spatial resolution or electromechanical uncoupling of the beating heart. To overcome this limitation, we herein introduce a scalable method for fabricating a tissue-like, high-density, fully elastic electrode (elastrode) array capable of achieving real-time, stable, cellular level-resolution electrophysiological mapping in vivo. Testing with acute rabbit and porcine models, the device is proven to have robust and intimate tissue coupling while maintaining its chemical, mechanical, and electrical properties during the cardiac cycle. The elastrode array records epicardial atrial signals with comparable efficacy to currently available endocardial-mapping techniques but with 2 times higher atrial-to-ventricular signal ratio and >100 times higher spatial resolution and can reliably identify electrical local heterogeneity within an area of simultaneously identified rotor-like electrical patterns in a porcine model of chronic AF.

Pial arteriovenous fistula resembling the vein of Galen aneurysmal malformation, treated with staged endovascular embolization: a case report.

A 41-month-old boy was presented to our hospital because of an intracranial mass suspected of cerebrovascular malformation. He was admitted and received cerebral angiography. The angiography result confirmed the intracranial mass was the dilated vein of Galen resulting from a pial arteriovenous fistula, which quite resembling the vein of Galen aneurysmal malformation. Considering one-time embolization of the fistula may greatly change the distribution of intracranial blood flow, we decided to perform staged embolization. In the first stage, we partially embolized the fistula, resulting in a sharp decrease in blood flow to the lesion. The second intervention was performed one month later, and completely embolized the fistula. The boy recoverd well and returned to normal childhood without any neurological deficits. Follow-up MR images obtained at 10 months after the last procedure showing total obliteration of the pAVF, gradually shrinking of the varix, and remodeling of the vein of Galen.

Parallel multi-swarm cooperative particle swarm optimization for protein-ligand docking and virtual screening.

BACKGROUND: A high-quality docking method tends to yield multifold gains with half pains for the new drug development. Over the past few decades, great efforts have been made for the development of novel docking programs with great efficiency and intriguing accuracy. AutoDock Vina (Vina) is one of these achievements with improved speed and accuracy compared to AutoDock4. Since it was proposed, some of its variants, such as PSOVina and GWOVina, have also been developed. However, for all these docking programs, there is still large room for performance improvement. RESULTS: In this work, we propose a parallel multi-swarm cooperative particle swarm model, in which one master swarm and several slave swarms mutually cooperate and co-evolve. Our experiments show that multi-swarm programs possess better docking robustness than PSOVina. Moreover, the multi-swarm program based on random drift PSO can achieve the best highest accuracy of protein-ligand docking, an outstanding enrichment effect for drug-like activate compounds, and the second best AUC screening accuracy among all the compared docking programs, but with less computation consumption than most of the other docking programs. CONCLUSION: The proposed multi-swarm cooperative model is a novel algorithmic modeling suitable for protein-ligand docking and virtual screening. Owing to the existing coevolution between the master and the slave swarms, this model in parallel generates remarkable docking performance. The source code can be freely downloaded from https://github.com/li-jin-xing/MPSOVina .

Antibiotic cocktail-induced gut microbiota depletion in different stages could cause host cognitive impairment and emotional disorders in adulthood in different manners.

Gut microbiota depletion may result in cognitive impairment and emotional disorder. This study aimed to determine the possible association between host gut microbiota, cognitive function, and emotion in various life stages and its related underlying mechanisms. Seventy-five neonatal mice were randomly divided into five groups (n = 15 per group). Mice in the vehicle group were administered distilled water from birth to death, and those in the last four groups were administered antibiotic cocktail from birth to death, from birth to postnatal day (PND) 21 (infancy), from PND 21 to 56 (adolescence), and from PND 57 to 84 (adulthood), respectively. Antibiotic exposure consistently altered the gut microbiota composition and decreased the diversity of gut microbiota. Proteobacteria were the predominant bacteria instead of Firmicutes and Bacteroidetes after antibiotic exposure in different life stages. Long-term and infant gut microbiota depletion resulted in anxiety- and depression-like behaviors, memory impairments, and increased expression of γ-aminobutyric acid type A receptor α1 of adult mice. Long-term antibiotic exposure also significantly decreased serum interleukin (IL)-1ß, IL-10, and corticosterone of adult mice. Gut microbiota depletion in adolescence resulted in anxiety-like behaviors, short-term memory decline, decreased serum interferon-γ (IFN-γ), mRNA expression of 5-hydroxytryptamine receptor 1A, and neuropeptide Y receptor Y2 in the prefrontal cortex of adult mice. Antibiotic exposure in adulthood damaged short-term memory and decreased serum IL-10, IFN-γ, and increased γ-aminobutyric acid type B receptor 1 mRNA expression of adult mice. These results suggest that antibiotic-induced gut microbiota depletion in the long term and infancy resulted in the most severe cognitive and emotional disorders followed by depletion in adolescence and adulthood. These results also suggest that gut microbes could influence host cognitive function and emotion in a life stage-dependent manner by affecting the function of the immune system, hypothalamic-pituitary-adrenal axis, and the expression of neurochemicals in the brain.

Heat-inactivated Lacticaseibacillus paracasei N1115 alleviates the damage due to brain function caused by long-term antibiotic cocktail exposure in mice.

Critical development period of intestinal microbiota occurs concurrently with brain development, and their interaction is influenced by the microbiota-gut-brain axis. This study examined how antibiotics exposure affected gut microbiota and brain development and analyzed the possible benefits of heat-inactivated Lacticaseibacillus paracasei N1115 (N1115). Thirty neonatal male mice were randomly divided into three groups and treated with sterilized water (control), an antibiotic cocktail (Abx), or antibiotics plus heat-inactivated N1115 (Abx + N1115) for 84 days. We found that while the mRNA levels of GABAAα1, GABAb1, and glucocorticoid receptor (GR) in the hippocampus and brain-derived neurotrophic factor (BDNF), GABAAα1, GABAb1, and nerve growth factor (NGF) in the prefrontal cortex were higher, the mRNA levels of 5-HT1A were lower in the Abx group. The Abx + N1115 group had lower mRNA levels of GABAAα1, GABAb1, and GR in the hippocampus and BDNF, GABAb1, and NGF in the prefrontal cortex than the Abx group. The latency period was longer in the Morris water maze test while longer rest time was seen in tail suspension test in the Abx group than the control and Abx + N1115 groups. In the open field test, the moving time and distance of the Abx group were reduced. Further, the alpha-diversity indexes of the Abx and Abx + N1115 groups were significantly lower than the control. Further, long-term exposure to antibiotics disrupted the intestinal microbiota as evidenced by decreased Bacteroides, Firmicutes, and Lactobacillus, and increased Proteobacteria and Citrobacter. However, N1115 significantly decreased the abundance of Citrobacter when compared with those in the Abx group. These results indicate that antibiotics can substantially damage the intestinal microbiota and cognitive function, causing anxiety and depression, which can be alleviated by heat-inactivated N1115 via modulation of the microbiota-gut-brain axis.

RDPSOVina: the random drift particle swarm optimization for protein-ligand docking.

Protein-ligand docking is of great importance to drug design, since it can predict the binding affinity between ligand and protein, and guide the synthesis direction of the lead compounds. Over the past few decades, various docking programs have been developed, some of them employing novel optimization algorithms. However, most of those methods cannot simultaneously achieve both good efficiency and accuracy. Therefore, it is worthwhile to pour the efforts into the development of a docking program with fast speed and high quality of the solutions obtained. The research presented in this paper, based on the docking scheme of Vina, developed a novel docking program called RDPSOVina. The RDPSOVina employes a novel search algorithm but the same scoring function of Vina. It utilizes the random drift particle swarm optimization (RDPSO) algorithm as the global search algorithm, implements the local search with small probability, and applies Markov chain mutation to the particles' personal best positions in order to harvest more potential-candidates. To prove the outstanding docking performance in RDPSOVina, we performed the re-docking experiments on two PDBbind datasets and cross-docking experiments on the Sutherland-crossdock-set, respectively. The RDPSOVina exhibited superior protein-ligand docking accuracy and better cross-docking prediction with higher operation efficiency than most of the compared methods. It is available at https://github.com/li-jin-xing/RDPSOVina .

Development of emergent ferroelectric nematic liquid crystals with highly fluorinated and rigid mesogens.

The emerging ferroelectric nematic liquid crystals have been attracting broader interests in new liquid crystal physics and their unique material properties. One big challenge for the ferroelectric nematic research is to enrich the material choice, which is now limited to RM734 and DIO families as representatives, in sharp contrast to the enormously diverse variety of the traditional apolar nematic liquid crystals. Here, we report a design of novel ferroelectric nematic materials with highly fluorinated and rigid mesogens. Noteworthily, they show distinct chemical structural features compared with previous aromatic ester-based molecules. The ferroelectric nematic phase was identified and confirmed through rigorous experiments. The bulk polarization was found to become purely along the long axis director, creating giant dielectric anisotropy. This work demonstrates a great potential for expanding ferroelectric nematic material diversity and will accelerate the corresponding application research and technology innovation.

Magnetic resonance imaging evaluation of the correlation between calcific tendinitis and rotator cuff injury.

BACKGROUND: This study aims to evaluate the incidence of calcific tendinitis (CaT) in rotator cuff tears (RCTs) and to assess the correlation between CaT and RCTs with magnetic resonance imaging (MRI). METHODS: The MRI of 108 patients with rotator cuff CaT admitted to our hospital from January 2019 to January 2021 were retrospectively analyzed. Another retrospective analysis was made of 108 patients with similar age, gender, occupation, and shoulder injury side to those in the first group. The incidence of RCTs and their correlation with CaT were assessed based on an MRI of shoulder joints. RESULTS: There was a statistical difference (p < 0.05) in the incidence of RCTs between the CaT group (23.4%) and the control group (37.2%). No significant difference was observed in the size of the RCTs between the two groups (P = 0.422). In the CaT group, 17.4% of patients had complete tears, compared with 26.3% in the control group. There was no significant correlation between the calcification site and RCTs in the CaT group, and only 3.7% of patients suffered calcification and a tear in the exact location of the same tendon (P > 0.05, r = 0.03). CONCLUSIONS: Compared with patients with shoulder pain without CaT, patients with rotator cuff CaT suffered no increased risk of RCTs on MRI, so CaT and RCTs may have different pathological causes, and there is no significant correlation between the two.

The transcription factors TLR1 and TLR2 negatively regulate trichome density and artemisinin levels in Artemisia annua.

The important antimalarial drug artemisinin is biosynthesized and stored in Artemisia annua glandular trichomes and the artemisinin content correlates with trichome density; however, the factors affecting trichome development are largely unknown. Here, we demonstrate that the A. annua R2R3 MYB transcription factor TrichomeLess Regulator 1 (TLR1) negatively regulates trichome development. In A. annua, TLR1 overexpression lines had 44.7%-64.0% lower trichome density and 11.5%-49.4% lower artemisinin contents and TLR1-RNAi lines had 33%-93.3% higher trichome density and 32.2%-84.0% higher artemisinin contents compared with non-transgenic controls. TLR1 also negatively regulates the expression of anthocyanin biosynthetic pathway genes in A. annua. When heterologously expressed in Arabidopsis thaliana, TLR1 interacts with GLABROUS3a, positive regulator of trichome development, and represses trichome development. Yeast two-hybrid and pull-down assays indicated that TLR1 interacts with the WUSCHEL homeobox (WOX) protein AaWOX1, which interacts with the LEAFY-like transcription factor TLR2. TLR2 overexpression in Arabidopsis and A. annua showed that TLR2 reduces trichome development by reducing gibberellin levels. Furthermore, artemisinin contents were 19%-43% lower in TLR2-overexpressing A. annua plants compared to controls. These data indicate that TLR1 and TLR2 negatively regulate trichome density by lowering gibberellin levels and may enable approaches to enhance artemisinin yields.

[Protective effect and mechanism of Bifidobacterium bifidum TMC3115 on long-term colitis in mice which exposed to antibiotic in early life].

OBJECTIVE: To explore the protective effect and mechanism of Bifidobacterium bifidum TMC3115 of improving the gut microbiota disorder caused by antibiotic exposurein early life, and the possible protection of inflammatory bowel disease in adulthood in mice. METHODS: 80 newborn mice were randomly divided into 3 groups, a blank control group(n=40), a ceftriaxone exposure group(n=20), a Bifidobacterium bifidum TMC3115 intervention group(n=20). After birth, they were respectively treated with saline, ceftriaxone(100 mg/kg), and ceftriaxone(100 mg/kg) + TMC3115(1×10~9CFU/d) for 3 weeks. After 3 weeks, half of each group was randomly sacrificed, and the rest were normally fed to 6 weeks. At 6 weeks, the blank control group was randomly divided into a negative control group(n=10) and a colitis model group(n=10). The negative control group drunk pure water freely, and the other three groups were added 3% DSS to the drinking water for 4 days to induce colitis. At 6 weeks and 4 days, the remaining mice were sacrificed. The weight change, spleen coefficient, gut microbiota analysis based on second-generation sequencing and serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-10(IL-10)levels of the mice at 3 weeks and after DSS intervention were recorded. In addition, the colon length and inflammation pathology score of the mice after DSS intervention were also measured. RESULTS: At 3 weeks, compared with the control, antibiotic exposure in the early life inhibited the weight gain and reduced the diversity and uniformity of the gut microbiota of the mice(P<0.05). The intervention of TMC3115 under antibiotic exposure during this period increased the relative abundance of Bifidobacterium in the intestines(P<0.05), and the effect still existed after DSS stimulation in adulthood, laying the foundation for TMC3115 to exert long-term benefits. After DSS stimulation in adulthood, mice showed significant weight gain inhibition, colon length shorteningand inflammation pathology scoreincrease compared with the negative control(P<0.05), showed the inflammatory bowel disease(IBD)model was successfully constructed. The relative abundance of beneficial bacteria such as Lactobacillus in the Bifidobacterium bifidum TMC3115 intervention group increased compared with the ceftriaxone exposure group(P<0.05), while the relative abundance of harmful bacteria such as Staphylococcus, Clostridium, and Desulfovibrio decreased(P<0.05). Furthermore, the mice exposed to antibiotic in early life produced a stronger immune response, but the mice which received TMC3115 intervention at the same time had a significant decrease in serum TNF-α and IL-6 levels and increase in IL-10 level compared with the mice which only interfered with antibiotics(P<0.05). CONCLUSION: Antibiotic exposure in early life is a negative factor for long-term inflammatory bowel disease, and TMC3115 has preventive significance for long-term inflammatory bowel disease under the background of antibiotic exposure. The mechanism of TMC3115 may be to adjust the gut microbiota and balance the immune system.