Association of clinicopathologic and sonographic features with stromal tumor-infiltrating lymphocytes in triple-negative breast cancer.

BACKGROUND: Increased level of stromal tumor-infiltrating lymphocytes (sTILs) are associated with therapeutic outcomes and prognosis in triple-negative breast cancer (TNBC). This study aimed to investigate the associations of clinicopathologic and sonographic features with sTILs level in TNBC. METHODS: This study included invasive TNBC patients with postoperative evaluation of sTILs after surgical resection. Tumor shape, margin, orientation, echo pattern, posterior features, calcification, and vascularity were retrospectively evaluated. The patients were categorized into high-sTILs (≥ 20%) and low-sTILs (< 20%) level groups. Chi-square or Fisher's exact tests were used to assess the association of clinicopathologic and sonographic features with sTILs level. RESULTS: The 171 patients (mean ± SD age, 54.7 ± 10.3 years [range, 22‒87 years]) included 58.5% (100/171) with low-sTILs level and 41.5% (71/171) with high-sTILs level. The TNBC tumors with high-sTILs level were more likely to be no special type invasive carcinoma (p = 0.008), higher histologic grade (p = 0.029), higher Ki-67 proliferation rate (all p < 0.05), and lower frequency of associated DCIS component (p = 0.026). In addition, the TNBC tumors with high-sTILs level were more likely to be an oval or round shape (p = 0.001), parallel orientation (p = 0.011), circumscribed or micro-lobulated margins (p < 0.001), complex cystic and solid echo patterns (p = 0.001), posterior enhancement (p = 0.002), and less likely to have a heterogeneous pattern (p = 0.001) and no posterior features (p = 0.002). CONCLUSIONS: This preliminary study showed that preoperative sonographic characteristics could be helpful in distinguishing high-sTILs from low-sTILs in TNBC patients.

Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis.

OBJECTIVE: The specific breast milk-derived metabolites that mediate host-microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. DESIGN: We enrolled 250 mother-infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings. RESULTS: The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacteria degraded mannan into mannose, consequently enhancing the mannan-dependent biosynthesis of O-antigen and lipopolysaccharide. Correlation analysis confirmed that in infants with AD, the abundance of Escherichia coli under high AA concentrations was positively correlated with some microbial pathways (eg, 'GDP-mannose-derived O-antigen and lipopolysaccharide biosynthesis'). These findings are consistent with those of the animal studies. Additionally, AA, but not EPA, disrupted the ratio of CD4/CD8 cells, increased skin lesion area and enhanced the proportion of peripheral Th2 cells. It also promoted IgE secretion and the biosynthesis of prostaglandins and leukotrienes in BALB/c mice fed AA following ovalbumin immunostimulation. Moreover, AA significantly increased IL-4 secretion in HaCaT cells costimulated with TNF-α and INF-γ. CONCLUSIONS: This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.

Subchronic oral toxic effects of 2,4-dinitroaniline in wistar rats: A comprehensive toxicity evaluation.

2,4-dinitroaniline (2,4-D), a widely used dye intermediate, is one of the typical pollutants, and its potential health risks and toxicity are still largely unknown. To explore its subchronic oral toxicity, Wistar rats (equal numbers of males and females) were used as test animals, and a 90-day oral dosing experiment was conducted, divided into control group, low-dose group (0.055 mg/kg), medium-dose group (0.22 mg/kg), medium-high dose group (0.89 mg/kg), and high-dose group (3.56 mg/kg). The body weight data, clinical appearance, and drug reactions of each test rat within 90 days of dosing were recorded; morning urine samples were collected four times to test for eight urinary indicators; blood samples were collected to test for nineteen hematological indicators and sixteen biochemical indicators; tissue samples were collected for pathological analysis; moreover, the no-observed-adverse-effect level (NOAEL) was determined, and the benchmark dose method was used to support this determination and provide a statistical estimate of the dose corresponding. The results indicated that the chronic toxicity of 2,4-dinitroaniline showed certain gender differences, with the eyes, liver, and kidneys being the main potential target organs of toxicity. Moreover, the subchronic oral NOAEL for 2,4-dinitroaniline was determined to be 0.22 mg/kg body weight (0.22 mg/kg for males and 0.89 mg/kg for females), and a preliminary calculation of the safe exposure limit for human was 0.136 mg/kg. The research results greatly enriched the safety evaluation data of 2,4-dinitroaniline, contributing to a robust scientific foundation for the development of informed safety regulations and public health precautions.

Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

Summary of best evidence for rehabilitation management of patients with motor dysfunction after stroke. / è„‘å’ä¸­è¿åŠ¨åŠŸèƒ½éšœç¢æ‚£è€ åº·å¤ç®¡ç†çš„æœ€ä½³è¯æ®æ€»ç»“.

OBJECTIVES: The rehabilitation work for patients with motor dysfunction after stroke is crucial. However, there is currently a lack of summarized evidence regarding the rehabilitation management of stroke patients in rehabilitation wards, communities, and at home. This study aims to compile relevant evidence on the rehabilitation management of patients with motor dysfunction after stroke, providing a reference for clinical and community health professionals to carry out rehabilitation interventions. METHODS: A systematic search was conducted in BMJ Best Practice, UpToDate, National Guidebook Clearinghouse, American Heart Association/American Stroke Association, Canadian Medical Association, National Institute for Health and Clinical Excellence, United States Department of Veterans Affairs/ Department of Defense, Registered Nurses Association of Ontario, JBI Evidence-Based Healthcare Center Database, The Cochrane Library, PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang Database, SinoMed, and other databases for all literature on the rehabilitation management of patients with motor dysfunction after stroke. This included clinical decision-making, guidelines, expert consensuses, recommended practices, systematic reviews, and evidence summaries, with the search period spanning from the establishment of each database to October 2023. Two researchers independently evaluated the quality of the literature. RESULTS: A total of twenty-one documents were included, consisting of 11 guidelines, 2 expert consensus, and 8 systematic reviews. Evidence was extracted and integrated from the included literature, summarizing forty-five pieces of evidence across nine areas: rehabilitation management model, rehabilitation institutions, rehabilitation teams, timing of rehabilitation interventions, rehabilitation assessment, rehabilitation programs, rehabilitation duration and frequency, rehabilitation intensity, and rehabilitation support These covered comprehensive rehabilitation management content for stroke patients in the early, subacute, and chronic phases. CONCLUSIONS: The best evidence summarized in this study for the rehabilitation management of patients with motor dysfunction after stroke is comprehensive and of high quality. It provides important guidance for clinical and community healthcare professionals in carrying out rehabilitation interventions. When applying the evidence, it is recommended to consider the current condition of the stroke patient, the extent of motor dysfunction, environmental factors, and the patient's preferences. Then, select the most appropriate rehabilitation plan, and adjust the type and intensity of training according to each patient's specific needs and preferences.

A novel simplified sonographic approach with fluoroscopy-controlled L5 transforaminal epidural injections in patients with high iliac crest: a retrospective study.

BACKGROUND: To explore a novel ultrasound (US) modality for lumbar transforaminal epidural injections (TFEIs) in patients with low back pain (LBP) and L5 radicular pain combined with high iliac crest (HIC). METHODS: One-hundred and forty-one patients were retrospectively stratified into two groups based on the treatment they received: novel group, receiving US-guided and fluoroscopy (FL)-controlled TFEIs using a sagittal oblique approach between the superior articular process of L5 and S1, and control group, receiving US-guided TFEIs with conventional transverse approach combined with FL confirmation. Accuracy of contrast dispersing into lumbar epidural space was set as the primary endpoint. Radiation dosages, procedure time, numeric rating scale (NRS) scores, Modified Oswestry Disability Questionnaire (MODQ) scores, adverse events, and rescue analgesic requirement were also recorded. The generalized liner mixed model (GLMMs) was employed to compare the repeatedly measured variables between groups, taking individual confounding factors as covariance. RESULTS: The accuracy of TFEIs was 92.8% and 65.2% in novel and control group, with a significant difference of 26.7% (95% CI: 15.4%, 39.8%) between two modalities (p < 0.001). Significant pain relief was observed in novel group as opposed to control group after one injection. Procedure time in novel group (8.4 ± 1.6 min) was shorter than control group (15.8 ± 3.5 min) (p < 0.001) with less radiation dosage (3047 ± 5670 vs. 8808 ± 1039 µGy/m2, p < 0.001). Significantly, lower incidence of L5 paresthesia occurred in novel group. Statistical differences of NRS scores between the novel and control group were reached at 1 week after procedure (1 (IQR: - 1-3) vs. 3 (IQR: - 1-7), p = 0.006), while not reached at both 1- (1 (IQR: 0-2) vs. 1 (IQR: - 1-3), p = 0.086) or 3-month follow-up (0 (IQR: - 1-1) vs. 1 (IQR: 0-2), p = 0.094). Both groups showed similar functional improvement (F = 0.103, p = 0.749) during follow-up. CONCLUSIONS: The novel sonographic technique provided superior accuracy needle placement and better pain-relieving effect through one injection as compared to the routine transverse approach. Consequently, in situations where the HIC imposed limitations for TFEIs performance on L5, the novel technique should be recommended to consider increasing accurate puncture, minimizing radiation exposure, consuming procedure time, and reducing the risk of neuraxial injury.

Analysis of factors influencing the recurrence of diabetic foot ulcers.

OBJECTIVE: The aim of this study is to investigate the factors influencing the recurrence of diabetic foot ulcers (DFU) and provide guidance for reducing the recurrence rate. METHODS: A total of 211 patients diagnosed with DFU who were hospitalized and discharged from the hospital from October 2015 to January 2020 were included as the study cohort. Participants were divided into two groups according to whether the foot ulcer recurred during the 2-year follow-up period: a recurrence group (n = 84) and a non-recurrence group (n = 127). The following data were collected and analyzed for the two groups of patients: general information, foot information, laboratory indicators, diabetes comorbidities, and complications. RESULTS: (1) The overall recurrence rate of diabetic foot ulcers (DFU) within 2 years was 39.8%, indicating a high recurrence rate. (2) Significant differences were observed between the two patient groups in terms of BMI, HbA1c, TBIL, CRP, financial situation, foot deformity, first ulcer on the sole of the foot, previous amputation history, Wagner grade of the first ulcer, osteomyelitis, DFU duration (>60 days), lower limb vascular reconstruction, peripheral arterial disease (PAD), and diabetic peripheral neuropathy (DPN) (t = 2.455; Z = -1.988, -3.731, -3.618; χ2 = 7.88, 5.004, 3.906, 17.178, 16.237, 5.007, 24.642, 4.782, 29.334, 10.253). No significant differences were found for the other indicators. (3) Logistic regression analysis revealed that TBIL (OR = 0.886, p = 0.036) was a protective factor against ulcer recurrence. In contrast, PAD, previous amputation history, DPN, and the first ulcer on the sole of the foot (OR = 3.987, 6.758, 4.681, 2.405; p < 0.05 or p < 0.01) were identified as risk factors for ulcer recurrence. CONCLUSION: Early screening and preventive education targeting high-risk factors such as DPN, PAD and the initial ulcer location on the sole of the foot are essential to mitigate the high long-term recurrence rate of DFU. Furthermore, the protective role of TBIL in preventing ulcer recurrence underscores the importance of monitoring bilirubin levels as part of a comprehensive management strategy for DFU patients.

Electricity generated by upstream proton diffusion in two-dimensional nanochannels.

The movement of ions along the pressure-driven water flow in narrow channels, known as downstream ionic transport, has been observed since 1859 to induce a streaming potential and has enabled the creation of various hydrovoltaic devices. In contrast, here we demonstrate that proton movement opposing the water flow in two-dimensional nanochannels of MXene/poly(vinyl alcohol) films, termed upstream proton diffusion, can also generate electricity. The infiltrated water into the channel causes the dissociation of protons from functional groups on the channel surface, resulting in a high proton concentration inside the channel that drives the upstream proton diffusion. Combined with the particularly sluggish water diffusion in the channels, a small water droplet of 5 µl can generate a voltage of ~400 mV for over 330 min. Benefiting from the ultrathin and flexible nature of the film, a wearable device is built for collecting energy from human skin sweat.

Mutation-Selected Amplification droplet digital PCR: A new single nucleotide variant detection assay for TP53R249S mutant in tumor and plasma samples.

The early detection of gene mutations in physiological and pathological processes is a powerful approach to guide decisions in precision medicine. However, detecting low-copy mutant DNA from clinical samples poses a challenge due to the enrichment of wild-type DNA backgrounds. In this study, we devised a novel strategy, named Mutation-Selected Amplification droplet digital PCR (MSA-ddPCR), to quantitatively analyze single nucleotide variants (SNVs) at low variant allele frequencies (VAFs). Using TP53R249S (a hotspot mutation associated with hepatocellular carcinoma) as a model, we optimized the concentration ratio of primers, the annealing temperature and nucleic acid amplification modifiers. Subsequently, we evaluated the linear range and precision of MSA-ddPCR by detecting TP53R249S and TP53wild-type (TP53WT) plasmid DNA, respectively. MSA-ddPCR demonstrated superior ability to discriminate between mutant DNA and wild-type DNA compared to traditional TaqMan-MGB PCR. We further applied MSA-ddPCR to analyze the TP53R249S mutation in 20 plasma samples and 15 formalin-fixed paraffin-embedded (FFPE) tissue samples, and assessed the agreement rates between MSA-ddPCR and amplicon high-throughput sequencing. The results showed that the limit of blanks of MSA-ddPCR are 0.449 copies µL-1 in the FAM channel and 0.452 copies µL-1 in the VIC channel. MSA-ddPCR could accurately quantify VAFs as low as 0.01 %, surpassing existing PCR and next-generation sequencing (NGS) methods. In the detection of clinical samples, a high correlation was found between MSA-ddPCR and amplicon high-throughput sequencing. Additionally, MSA-ddPCR outperformed sequencing methods in terms of detection time and simplicity of data analysis. MSA-ddPCR can be easily implemented into clinical practice and serve as a robust tool for detecting mutant genes due to its high sensitivity and accuracy.

[Effects of "brain-gut coherence" method of acupuncture on motor function and intestinal microflora in the patients with cerebral ischemic stroke].

OBJECTIVE: To observe the clinical effect of "brain-gut coherence" method of acupuncture on cerebral ischemic stroke (CIS) and explore its action mechanism. METHODS: A total of 82 patients with CIS were randomly divided into an observation group (41 cases, 3 cases dropped out, 2 cases discontinued) and a control group (41 cases, 4 cases dropped out, 2 cases excluded). The conventional basic treatment was administered in the two groups. Additionally, in the observation group, "brain-gut coherence" method of acupuncture was delivered. The stimulating points included the parietal and temporal anterior oblique line on the affected side, Zhongwan (CV 12), Guanyuan (CV 4), and bilateral Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, the routine acupuncture was operated at Baihui (GV 20), Yintang (GV 24+), bilateral Fengchi (GB 20) and Zusanli (ST 36), and Hegu (LI 4), Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5), Futu (ST 32), Sanyinjiao (SP 6) and Taichong (LR 3) on the affected side. Acupuncture stimulation lasted 30 min each time, once daily, and for 5 days a week. The intervention for 4 weeks was required. The scores of Fugl-Meyer assessment scale (FMA), Berg balance scale (BBS) and the modified Barthel index (MBI), as well as the score of gastrointestinal symptoms were compared before and after treatment in the two groups. The neutrophil count (NUE) and the content of the serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected before and after treatment in the two groups. Using 16S rRNA gene sequencing, the structure and relative abundance of intestinal microflora was detected before and after treatment; and with the enzyme linked immunosorbent assay (ELISA) adopted, the levels of intestinal fatty acid-binding protein (iFABP), D-lactate (D-LA), lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), tumor necrosis factor-α(TNF-α), interleukin (IL)-1ß and IL-6 in the serum were detected before and after treatment in the two groups. RESULTS: After treatment, the scores of FMA, BBS and MBI were increased (P<0.05), and the scores of gastrointestinal symptoms were decreased (P<0.05) compared with those before treatment in the two groups. Compared with the control group, the scores of FMA, BBS and MBI were higher (P<0.05) and the score of gastrointestinal symptoms was lower (P<0.05) in the observation group after treatment. NEU and the content of serum NT-proBNP were reduced in the two groups (P<0.05), and the content of serum NT-proBNP in the observation group was lower than that of the control group (P<0.05) after treatment. Chao1, Ace, Sobs and Shannon indexes were increased after treatment compared with those before treatment in the two groups (P<0.05); and these indexes in the observation group were higher when compared with the control group (P<0.05). After treatment, the relative abundance of Bacteroidaceae, Enterobacteriaceae, Oscillospiraceae, Streptococcaceae and Sutterellaceae was reduced in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was lower in the observation group when compared with the control group (P<0.05). After treatment, the relative abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and Coriobacteriaceae was increased in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was elevated in the observation group when compared with the control group (P<0.05). After treatment, the levels of iFABP, D-LA, LPS, LBP, TNF-α, IL-1ß and IL-6 were reduced when compared with those before treatment in the two groups (P<0.05), and these levels of the observation group were lower than those of the control group (P<0.05). CONCLUSION: "Brain-gut coherence" method of acupuncture can improve the motor function and gastrointestinal function of the patients with cerebral ischemic stroke, which may be related to modulating the structure of intestinal microflora, alleviating inflammatory reactions and accelerating the intestinal barrier repair.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

Asperuloside inhibits the activation of pancreatic cancer-associated fibroblasts via activating transcription factor 6.

BACKGROUND: Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress. METHOD: CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C-C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP. CONCLUSION: ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment.

A near-infrared fluorescent probe for imaging peroxynitrite levels in paw edema mice and drug evaluation.

A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO- in living cells, image ONOO- in paw edema mice and evaluate anti-inflammatory drugs.

Decorin in the spatial control of collagen mineralization.

Understanding the molecular mechanism by which the periodontal ligament (PDL) is maintained uncalcified between two mineralized tissues (cementum and bone) may facilitate the functional repair and regeneration of the periodontium complex, disrupted in the context of periodontal diseases. However, research that explores the control of type I collagen (COL I) mineralization fails to clarify the detailed mechanism of regulating spatial collagen mineralization, especially in the periodontium complex. In the present study, decorin (DCN), which is characterized as abundant in the PDL region and rare in mineralized tissues, was hypothesized to be a key regulator in the spatial control of collagen mineralization. The circular dichroism results confirmed that DCN regulated the secondary structure of COL I, and the surface plasmon resonance results indicated that COL I possessed a higher affinity for DCN than for other mineralization promoters, such as DMP-1, OPN, BSP and DSPP. These features of DCN may contribute to blocking intrafibrillar mineralization in COL I fibrils during the polymer-induced liquid-precursor mineralization process when the fibrils are cross-linked with DCN. This effect was more remarkable when the fibrils were phosphorylated by sodium trimetaphosphate, as shown by the observation of a tube-like morphology via TEM and mineral sheath via SEM. This study enhances the understanding of the role of DCN in mineralization regulation among periodontal tissues. This provides insights for the development of biomaterials for the regeneration of interfaces between soft and hard tissues.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

Optimized expression of Peptidyl-prolyl cis/transisomerase cyclophilinB with prokaryotic toxicity from Sporothrix globosa.

Cyclophilin B (CypB), a significant member of immunophilins family with peptidyl-prolyl cis-trans isomerase (PPIase) activity, is crucial for the growth and metabolism of prokaryotes and eukaryotes. Sporothrix globosa (S. globosa), a principal pathogen in the Sporothrix complex, causes sporotrichosis. Transcriptomic analysis identified the cypB gene as highly expressed in S. globosa. Our previous study demonstrated that the recombinant Escherichia coli strain containing SgcypB gene failed to produce sufficient product when it was induced to express the protein, implying the potential toxicity of recombinant protein to the bacterial host. Bioinformatics analysis revealed that SgCypB contains transmembrane peptides within the 52 amino acid residues at the N-terminus and 21 amino acids near the C-terminus, and 18 amino acid residues within the cytoplasm. AlphaFold2 predicted a SgCypB 3D structure in which there is an independent PPIase domain consisting of a spherical extracellular part. Hence, we chose to express the extracellular domain to yield high-level recombinant protein with PPIase activity. Finally, we successfully produced high-yield, truncated recombinant CypB protein from S. globosa (SgtrCypB) that retained characteristic PPIase activity without host bacterium toxicity. This study presents an alternative expression strategy for proteins toxic to prokaryotes, such as SgCypB. ONE-SENTENCE SUMMARY: The recombinant cyclophilin B protein of Sporothrix globosa was expressed successfully by retaining extracellular domain with peptidyl-prolyl cis-trans isomerase activity to avoid toxicity to the host bacterium.

Precycling Strategy in Suitable Voltage to Improve the Stability of Interfacial Film and Suppress the Decline of LiNi0.6Mn0.2Co0.2O2 Cathode at Elevated Temperatures.

Layered ternary oxide LiNixMnyCo1-x-yO2 is a promising cathode candidate for high-energy lithium-ion batteries (LIBs). However, the capacity of LIBs is significantly restricted by several factors, including the repeated dissolution-regeneration of the interfacial film at high temperatures, the dissolution of transition metals, and the increase of impedance. Herein, a new precycling strategy in suitable voltage scope at room temperature is proposed to construct a uniform, thermally stable, and insoluble cathode-electrolyte interface (CEI), which helps to maintain stable cycling performances at high temperatures. Specifically, after 5 precycles in the range of 3.85-4.3 V at room temperature, a CEI layer containing numerous inorganic components and oligomers is formed on the surface of LiNi0.6Mn0.2Co0.2O2. Subsequently, the harmful side reactions are effectively suppressed, endowing the cell with an excellent capacity retention of 84.67% after 50 cycles at 0.5C and 55 °C, much higher than that of 65.61% under the conventional film-forming process conditions. This work emphasizes the crucial role of the precycling strategy in regulating the characteristics of CEI layer on the surface of cathode electrode, opening up a new avenue for the high-temperature application of positive electrodes of LIBs.

Near-infrared fluorescent probe for the imaging of viscosity in fatty liver mice and valuation of drug efficacy.

Fatty liver disease affects at least 25 percent of the population worldwide and is a severe metabolic syndrome. Viscosity is closely related to fatty liver disease, so it is urgent to develop an effective tool for monitoring viscosity. Herein, a NIR fluorescent probe called MBC-V is developed for imaging viscosity, consisting of dimethylaniline and malonitrile-benzopyran. MBC-V is non-fluorescent in low viscosity solutions due to intramolecular rotation. In high viscosity solution, the intramolecular rotation of MBC-V is suppressed and the fluorescence is triggered. MBC-V has long emission wavelength at 720 nm and large Stokes shift about 160 nm. Moreover, MBC-V can detect changes in cell viscosity in fatty liver cells, and can image the therapeutic effects of drug in fatty liver cells. By taking advantage of NIR emission, MBC-V can be used as an imaging tool for fatty liver disease and a way to evaluate the therapeutic effect of drug for fatty liver disease.

The effects of demand-resource relationship on work-family conflict under Chinese culture: a cross-sectional study.

Chinese work and lifestyle are undergoing dramatic changes caused by constantly changing technology and new policies. The demand-resource dynamic relationship, which leads to work-family conflict (WFC), has become increasingly complicated. However, very little is known about the combined effects of different factors from work and family spheres on WFC. This study aims to explore (1) the discrepancy between fit and misfit, (2) the discrepancy of the different degrees of fit, and (3) the discrepancy of the different degrees of misfit from two perspectives: work demand-family resource and work resource-family demand. Data were collected from 745 individuals in China and analyzed using polynomial regression and response surface. The results demonstrate that individuals having low work demand-high family resources experience the lowest WFC, and the fit between work demands and family resources impacts the conflict in a U way. Similarly, high work resource-low family demand results in the lowest WFC; however, the fit between work resources and family demands has negative effects on the conflict. This study took factors from both family and work domains into consideration and explored the effect of their interaction on WFC. By examining the dynamic relationship between demands and resources, adjustments can be made in both domains simultaneously, providing more flexible guidance for management practices that reduce WFC.