High-Performance Ultraviolet Organic Light-Emitting Diodes Enabled by Double Boron-Oxygen-Embedded Benzo[m]tetraphene Emitters.

Ultraviolet organic light-emitting diodes (UV OLEDs) have attracted increasing attention because of their promising applications in healthcare, industry, and agriculture; however, their development has been hindered by the shortage of robust UV emitters. Herein, we embedded double boron-oxygen units into nonlinear polycyclic aromatic hydrocarbons (BO-PAHs) to regulate their molecular configurations and excited-state properties, enabling novel bent BO-biphenyl (BO-bPh) and helical BO-naphthyl (BO-Nap) emitters with hybridized local and charge-transfer (HLCT) characteristics. They could be facilely synthesized in gram-scale amounts via a highly efficient two-step route. BO-bPh and BO-Nap showed strong UV and violet-blue photoluminescence in toluene with full width at half-maximum values of 25 and 37 nm, along with quantum efficiencies of 98 and 99%, respectively. A BO-bPh-based OLED showed high color purity UV electroluminescence peaking at 394 nm with Commission Internationale de l'Eclairage (CIE) coordinates of (0.166, 0.021). Moreover, the device demonstrated a record-high maximum external quantum efficiency (EQE) of 11.3%, achieved by successful hot exciton utilization. This work demonstrates the promising potential of double BO-PAHs as robust emitters for future UV OLEDs.

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.

Overexpression of forebrain PTP1B leads to synaptic and cognitive impairments in obesity.

Obesity has reached pandemic proportions and is a risk factor for neurodegenerative diseases, including Alzheimer's disease. Chronic inflammation is common in obese patients, but the mechanism between inflammation and cognitive impairment in obesity remains unclear. Accumulative evidence shows that protein-tyrosine phosphatase 1B (PTP1B), a neuroinflammatory and negative synaptic regulator, is involved in the pathogenesis of neurodegenerative processes. We investigated the causal role of PTP1B in obesity-induced cognitive impairment and the beneficial effect of PTP1B inhibitors in counteracting impairments of cognition, neural morphology, and signaling. We showed that obese individuals had negative relationship between serum PTP1B levels and cognitive function. Furthermore, the PTP1B level in the forebrain increased in patients with neurodegenerative diseases and obese cognitive impairment mice with the expansion of white matter, neuroinflammation and brain atrophy. PTP1B globally or forebrain-specific knockout mice on an obesogenic high-fat diet showed enhanced cognition and improved synaptic ultrastructure and proteins in the forebrain. Specifically, deleting PTP1B in leptin receptor-expressing cells improved leptin synaptic signaling and increased BDNF expression in the forebrain of obese mice. Importantly, we found that various PTP1B allosteric inhibitors (e.g., MSI-1436, well-tolerated in Phase 1 and 1b clinical trials for obesity and type II diabetes) prevented these alterations, including improving cognition, neurite outgrowth, leptin synaptic signaling and BDNF in both obese cognitive impairment mice and a neural cell model of PTP1B overexpression. These findings suggest that increased forebrain PTP1B is associated with cognitive decline in obesity, whereas inhibition of PTP1B could be a promising strategy for preventing neurodegeneration induced by obesity.

Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Patients.

BACKGROUND Severe anemia caused by hemorrhoidal hematochezia is typically treated preoperatively with reference to severe anemia treatment strategies from other etiologies. This retrospective cohort study included 128 patients with hemorrhoidal severe anemia admitted to 3 hospitals from September 1, 2018, to August 1, 2023, and aimed to evaluate preoperative blood transfusion requirements. MATERIAL AND METHODS Of 5120 patients with hemorrhoids, 128 (2.25%; male/female: 72/56) experienced hemorrhoidal severe anemia, transfusion, and Milligan-Morgan surgery. Patients were categorized into 2 groups based on their preoperative hemoglobin (PHB) levels after transfusion: PHB ≥70 g/L as the liberal-transfusion group (LG), and PHB <70 as the restrictive-threshold group (RG). The general condition, bleeding duration, hemoglobin level on admission, transfusion volume, length of stay, immune transfusion reaction, surgical duration, and hospitalization cost were compared between the 2 groups. RESULTS Patients with severe anemia (age: 41.07±14.76) tended to be younger than those with common hemorrhoids (age: 49.431±15.59 years). The LG had a significantly higher transfusion volume (4.77±2.22 units), frequency of immune transfusion reactions (1.22±0.58), and hospitalization costs (16.69±3.31 thousand yuan) than the RG, which had a transfusion volume of 3.77±2.09 units, frequency of immune transfusion reactions of 0.44±0.51, and hospitalization costs of 15.00±3.06 thousand yuan. Surgical duration in the LG (25.69±14.71 min) was significantly lower than that of the RG (35.24±18.72 min). CONCLUSIONS Patients with hemorrhoids with severe anemia might require a lower preoperative transfusion threshold than the currently recognized threshold, with an undifferentiated treatment effect and additional benefits.

IL-1ß/IL-1R1 signaling is involved in the propagation of α-synuclein pathology of the gastrointestinal tract to the brain.

The pathological hallmark of Parkinson's disease (PD) is the intraneuronal accumulation of misfolded alpha-synuclein (termed Lewy bodies) in dopaminergic neurons of substantia nigra par compacta (SNc). It is assumed that the α-syn pathology is induced by gastrointestinal inflammation and then transfers to the brain by the gut-brain axis. Therefore, the relationship between gastrointestinal inflammation and α-syn pathology leading to PD remains to be investigated. In our study, rotenone (ROT) oral administration induces gastrointestinal tract (GIT) inflammation in mice. In addition, we used pseudorabies virus (PRV) for tracing studies and performed behavioral testing. We observed that ROT treatments enhance macrophage activation, inflammatory mediator expression, and α-syn pathology in the GIT 6-week post-treatment (P6). Moreover, pathological α-syn was localized with IL-1R1 positive neural cells in GIT. In line with these findings, we also find pS129-α-syn signals in the dorsal motor nucleus of the vagus (DMV) and tyrosine hydroxylase in the nigral-striatum dynamically change from 3-week post-treatment (P3) to P6. Following that, pS129-α-syn was dominant in the enteric neural cell, DMV, and SNc, accompanied by microglial activation, and these phenotypes were absent in IL-1R1r/r mice. These data suggest that IL-1ß/IL-1R1-dependent inflammation of GIT can induce α-syn pathology, which then propagates to the DMV and SNc, resulting in PD.

Internal Orifice Alloy Closure: A New Procedure for Treatment of Perianal Fistulizing Crohn's Disease.

BACKGROUND The high recurrence rate of perianal fistula Crohn's disease (PFCD) increases the need to protect the anal sphincter during each surgical treatment of fistulas. We aimed to evaluate the safety and efficacy of internal orifice alloy closure in patients with PFCD. MATERIAL AND METHODS Fifteen patients with PFCD were enrolled in the study between July 6, 2021, and April 27, 2023. All patients underwent preoperative colonoscopy and anal magnetic resonance examination for diagnosis and evaluation. Internal orifice alloy closure (IOAC) was performed only when Crohn's disease was in remission. The external sphincter had not been severed. Perianal magnetic resonance imaging examination was used for postoperative evaluation after 6 months. Fistula cure rate, length of stay, perianal pain, and Wexner incontinence score were retrospectively compared between 15 patients treated with IOAC and 40 patients treated with other surgical methods. RESULTS Fifteen patients (male/female: 9/6, age: 23.6±14.3 years) with PFCD were included (follow-up: 24 months). In total, 20.0% (3) had multiple tracts, and 13.3% (2) had a high anal fistula. Among them, 10 patients received biologics for induction for mucosal healing before surgery. The fistula healed completely in 80.0% (12/15) and did not heal in 20.0% (3/15). Three patients who did not heal underwent fistulotomy and eventually recovered. IOAC is not superior in terms of fistula healing rates, length of stay, and anal pain, but its Wexner incontinence scores are significantly lower than with other surgical methods. CONCLUSIONS IOAC is a novel sphincter-saving surgery that is effective and safe for the treatment of PFCD.

Tetradentate Platinum(II) and Palladium(II) Complexes Containing Fused 6/6/6 or 6/6/5 Metallocycles with Azacarbazolylcarbazole-Based Ligands.

A series of novel tetradentate Pt(II) and Pd(II) complexes containing fused 6/6/6 or 6/6/5 metallocycles employing azacarbazolylcarbazole (ACzCz)-based ligands was developed. Systematic experimental and theoretical studies suggest that both the ligand structures and the central metal ions have great influences on the electrochemical and photophysical properties of the complexes. The time-dependent density functional theory (TD-DFT) calculations and natural transition orbital (NTO) analyses reveal that the Pt(II) complexes possess 10.8-15.2% metal-to-ligand charge transfer (3MLCT) mixed with ligand-centered (3LC) characters, by contrast, the Pd(II) complexes exhibit significantly decreased 4.2-7.1% 3MLCT characters and enhanced 3LC compositions. All of the Pt(II) and Pd(II) complexes possess various channels for the intersystem crossing (ISC) on the basis of small energy gaps ΔES1-Tn and matching transition orbital compositions; moreover, Pd(ACzCz-1) and Pd(ACzCz-2) also possess efficient reverse intersystem crossing (RISC) to show both delayed fluorescence (DF) and phosphorescence in PMMA films at room temperature (RT). Pt(ACzCz-3) has ΦPL values of 57% with a τ of 5.1 µs in dichloromethane at RT and 50% with 3.9 µs in PMMA at RT. Notably, Pd(ACzCz-1) exhibits ultralong low-temperature phosphorescence with a τ of 1307 µs. Pt(ACzCz-2)-based green OLED employing 26mCPy as the host demonstrated a peak EQE of 8.2% and a Lmax of 24065 cd/m2.

Computational Studies on the Mechanism and Origin of the Different Regioselectivities of Manganese Porphyrin-Catalyzed C-H Bond Hydroxylation and Amidation of Equilenin Acetate.

The manganese porphyrin-catalyzed C-H bond hydroxylation and amidation of equilenin acetate developed by Breslow and his co-worker have been investigated with density functional theory (DFT) calculations. The hydroxylation of C(sp2)-H bond of equilenin acetate leading to the 6-hydroxylated product is more favorable than the hydroxylation of C(sp3)-H bond of equilenin acetate, leading to the 11ß-hydroxylation product. The computational results suggest that the C(sp2)-H bond hydroxylation of equilenin acetate undergoes an oxygen-atom-transfer mechanism, which is more favorable than the C(sp3)-H bond hydroxylation undergoing the hydrogen-atom-abstraction/oxygen-rebound (HAA/OR) mechanism by 1.6 kcal/mol. That is why, the 6-hydroxylated product is the major product and the 11ß-hydroxylated product is the minor product. In contrast, the 11ß-amidated product is the only observed product in manganese porphyrin-catalyzed amidation reaction. The benzylic amidation undergoes a hydrogen-atom-abstraction/nitrogen-rebound (HAA/NR) mechanism, in which hydrogen atom abstraction is followed by nitrogen rebound, leading to the 11ß-amidated product. The benzylic C(sp3)-H bond amidation at the C-11 position is more favorable than aromatic amidation at the C-6 position by 4.9 kcal/mol. Therefore, the DFT computational results are consistent with the experiments that manganese porphyrin-catalyzed C-H bond hydroxylation and amidation of equilenin acetate have different regioselectivities.

Phosphorescent Tetradentate Platinum(II) Complexes Containing Fused 6/5/5 or 6/5/6 Metallocycles.

A series of phenylpyridine (ppy)-based 6/5/5 N*C^N^O and biphenyl (bp)-based 6/5/6 N*C^C*N Pt(II) complexes employing tetradentate ligands with nitrogen or oxygen atoms as bridging groups have been developed. Ligand structural modifications have great influences on the electrochemical, photophysical, and excited-state properties, as well as photostabilities of the Pt(II) complexes, which were systematically studied by experimental and theoretical investigations. The time-dependent density functional theory calculations and natural transition orbital analyses reveal that Pt(bp-6), Pt(bp-7), and Pt(bp-8) have dominant ligand-centered (3LC) mixed with small metal-to-ligand charge-transfer (3MLCT) characters in T1 states, resulting in relatively low quantum efficiencies (ΦPL) of 5-33% and 12-32% in dichloromethane solution and PMMA film, respectively. By contrast, Pt(ppy-1) possesses much more 3MLCT character in the T1 state, enabling a high ΦPL of 95% in dichloromethane and 90% in DPEPO film, and large radiative decay rates. The strength of the Pt-N1 coordination bond plays a critical role in the photostability. Pt(ppy-1)- and Pt(bp-6)-doped polystyrene films demonstrate long photostability lifetimes of 150 min for LT97 and LT98.5, respectively. A Pt(ppy-1)-based green OLED using 26mCPy as host realized a peak EQE of 18.5%, which still maintained an EQE of 10.4% at 1000 cd/m2, and an Lmax of over 40 000 cd/m2 was achieved. This study should provide a valuable reference for the further development of efficient and stable phosphorescent Pt(II) complexes.

Understanding the structures and aromaticity of heteroporphyrins with computations.

Heteroporphyrins are porphyrin derivatives with replacement of the pyrrolic NH moiety by other heteroatom-containing groups, such as PH, AsH, SiH2, O, S, etc. For all studied heteroporphyrins, the macrocycle structure is distorted due to the presence of large heteroatoms. The HOMO-LUMO gap of heteroporphyrins is generally decreased compared to regular porphyrins. Both nucleus independent chemical shifts values and visualized anisotropy of induced current density were computed to describe the aromaticity of heteroporphyrins. The plots of anisotropy of induced current density suggest that the ring current diverged into an outer and an inner pathway at each ring. The current mainly passes through the outer path at the pyrrolic rings with inner hydrogen and through the inner path at the pyrrolic rings without inner hydrogen. In both regular porphyrin and O-substituted heteroporphyrins, the aromatic pathway is mainly contributed by the 22π-electron aromatic route model. Heteroatoms such as PH, AsH, S, Se and Te have little contribution to the aromaticity of heteroporphyrins. In addition, the π conjugation is also interrupted at the CH2 and SiH2 moiety, and the ring current mainly passes through the outer path of the heteroporphyrins with CH2 and SiH2 replacing the pyrrolic NH moiety. Therefore the 18π-[18]annulene model is dominated in PH-, AsH-, S-, Se-, Te-, CH2- and SiH2-substituted heteroporphyrins. These computational studies shed new light on the aromatic characters of heteroporphyrins, and will facilitate the further development of various novel heteroporphyrins.

First Report of Colletotrichum cereale Causing Anthracnose on Avena nuda in China.

Naked oats (Avena nuda L.) is rich in protein, fat, vitamin, mineral elements and so on, and is one of the world's recognized cereal crops with the highest nutritional and healthcare value. In July 2019, leaf spot was detected on A. nuda in Zhangbei experimental station of Hebei Agricultural University. The incidence of disease is 10% to 20%. The symptoms were similar to anthracnose disease, the infected leaves had fusiform or nearly fusiform yellowish-brown spots, yellow halo around the spots. Numerous acervuli with black setae diagnostic of fungi in the genus Colletotrichum were present on necrotic lesions. To identify the pathogen, ten symptomatic leaves were collected, and only one disease spot was isolated from each leaf. Small square leaf pieces (3 to 5 mm) were excised from the junction of diseased and healthy tissues with a sterile scalpel and surface disinfested with 75% alcohol for 30s, 0.1% corrosive sublimate for 1 min, rinsed three times in sterile water. Plant tissues were then transferred on potato dextrose agar (PDA), and incubated at 25°C for 7 days. Two fungal isolates were obtained and purified by single-spore isolation method. All fungi have the same morphology and no other fungi were isolated. The aerial mycelium was gray black. The conidia were colorless and transparent, falcate, slightly curved, tapered toward the tips, and produced in acervuli with brown setae. The length and width of 100 conidia were measured and size ranged from 1.86 to 3.84 × 8.62 to 29.81 µm. These morphological characteristics were consistent with the description of Colletotrichum cereale (Crouch et al. 2006). To further assess the identity of the species, the genomic DNA of two fungal isolates (LYM19-4 and LYM19-10) was extracted by a CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region as well as, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), and the beta-tubulin 2 (Tub2) partial genes were amplified and sequenced with primers ITS4/5, GDF/GDR, ACT-512F/ACT-783R, and T1/Bt2b, respectively (Carbone et al. 1999; Templeton et al. 1992; O'Donnell et al. 1997; Glass et al. 1995). The sequences of the ITS-rDNA region (MW040121, MW040122), the GAPDH sequences (MW052554, MW052555), the ACT sequences (MW052556, MW052551) and the Tub2 sequences (MW052552, MW052553) of the two single-spore isolates were more than 99% identical to C. cereale isolate CGMCC3.15110 (JX625159, KC843517, KC843534 and JX625186). Maximum likelihood tree based on concatenated sequences of the four genes were constructed using MEGA7. The results showed the strains isolated from A. nuda were closely related to C. cereale, as supported by high bootstrap values. A pathogenicity test of the C. cereale isolates was performed on first unfolding leaves of A. nuda. Koch's postulates were carried out with isolates by spraying a conidial suspension of 106 conidia/mL on leaves of healthy A. nuda. Four replicated pots were inoculated at a time, 10 leaves each pot, while sterile distilled water was used as the control. All treated plants were placed in a moist chamber (25°C, 16-h light and 8-h dark period). Anthracnose symptoms developed on the inoculated plants 7 days post inoculation while all control plants remained healthy. Microscopic examination showed the surface of infected leaves had the same acervuli, setae, and conidia as the original isolate. The pathogenicity test was repeated three times. C. cereale was previously reported as the causal agent of anthracnose on feather reed grass in US (Crouch et al. 2009). To our knowledge, this is the first report of C. cereale as the causal agent of A. nuda anthracnose in China.

First Report of Alternaria alternata Causing Leaf Spot on Avena nuda in Zhangbei, China.

Naked oats (Avena nuda L.) is an independent species of Avena, which can be used as both food and forage for rich nutritional value. In August 2019, leaf spot was observed at a naked oats planting base in Zhangbei County, Zhangjiakou City, Hebei Province. The incidence of disease was 40% to 50%. The symptoms of the lesions were chlorosis and gradually developing light brown spots with light yellow halos. The spots were irregular, enlarged and even coalesced to form large areas of necrosis on leaves. To identify the pathogen, twenty symptomatic leaves were collected, and one disease spot was isolated from each samples. Small square leaf pieces (3 to 5 mm) were excised from the junction of diseased and healthy tissues with a sterile scalpel and were sterilized with 75% alcohol for 30s, 0.1% mercuric chloride solution for 1 min, and then rinsed three times with sterile water, then transferred cultured on potato dextrose agar (PDA) at 25°C for 7 days. Four fungal isolates were obtained and purified by single-spore isolation method. All fungi have the same morphology and no other fungi were isolated. Colonies of the isolates had round margins, and thick fluffy aerial mycelia with brown coloration after 7 days on PDA. Conidiophores were brown, straight or flexuous, septate, single or in clusters. Conidia were obclavate or oval, dark brown, and size ranging from 4.61 to 15.68 × 6.61 to 35.49µm (n=100), with longitudinal and transverse septa varying from 1 to 3 and 1 to 7, respectively. The transverse median septum of the central section was especially thick. On the basis of morphological characteristics, the isolates were identified as Alternaria spp. (Simmons 2007). To further assess the identity of the species, the genomic DNA of pathogenic isolate (YM3) was extracted by CTAB protocol. The ribosomal DNA internal transcribed spacer (ITS) region, the glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the RNA polymerase II second largest subunit (RPB2), and the plasma membrane ATPase genes were amplified and sequenced with primers ITS1/4, gpd1/2, RPB2-6F/7cR and ATPDF1/ATPDR1 respectively (Nishikawa and Nakashima 2015; Woudenberg et al. 2015). Sequences of ITS, GAPDH, RPB2 and ATPase (MN646900, MT233043, MT233042, MN640794) of the isolate was 99.82%, 99.68%, 100% and 99.51% similar to the fungus A. alternata (MK461082.1, MK451978, KP124770.1, MK804115). A neighbor-joining phylogenetic tree was constructed by combining all sequenced loci in MEGA7. The isolate YM3 clustered in the A. alternata clade with 100% bootstrap support. Therefore, the pathogen was identified as A. alternata based on the morphological characteristics and molecular identification. A pathogenicity test of the A. alternata isolates was performed by placing mycelial disks (5 mm) with conidia on the surface of the first unfolding leaves of naked oats. Each leaf was inoculated with three disks. The pathogenicity test was repeated four times, and 10 leaves were inoculated in each repetition, while sterile PDA was used as the control. All treated plants were placed in a moist chamber (25°C, 16-h light and 8-h dark period). Leaf spot symptoms developed on the inoculated plants about 10 days post inoculation while all control plants remained healthy. The similar isolates were re-isolated from the inoculated and infected leaves and identified as A. alternata by DNA sequencing, fulfilling Koch's postulates. It has been reported that A. alternata can cause leaf spots on A. Sativa(Chen et al. 2020). However, to our knowledge, this is the first report of A. alternata causing leaf spots on A. nuda in China. It can be concluded that A. alternata can cause leaf spot disease of oats (A. Sativa and A. nuda). The spots disease is worthy of our attention for its harm to the production of oats.

[Analgesic effect of buccal acupuncture on acute arthritis in rabbits and underlying mechanisms].

OBJECTIVE: To observe the analgesic effect of acupuncture and to explore its central analgesic mechanism in rheumatoid arthritis rabbits.
 Methods: A total of 60 flap-eared white rabbits were randomly assigned into a normal control group (n=6), a model group (n=6), a body-acupuncture group (n=24), and a buccal acupuncture group (n=24). The later 2 groups were further randomly assigned into 0, 0.5, 1, and 2 h subgroups, with 6 cases in each group. The rheumatoid arthritis model was established by induction of egg-albumin. In the body acupuncture group, bilateral "Xiyan" and "Zusanli" were punctured for 15 s while in the buccal acupuncture group, acupuncture was applied to "Xi" for 15 s, with the needle retaining for 30 min. The pain threshold was detected with PL-200, taking struggle movements of rabbits as a measurement index, response latency from irradiation to struggling movements as the rabbit's pain threshold. The contents of ß-endorplhin (ß-EP) and cholecystokinin-8 (CCK-8) in cerebrospinal fluid were examined by radioimmunoassay.
 Results: Compared with the control group, pain threshold and CCK-8 levels decreased significantly (P<0.01) and the concentration of ß-EP significantly increased (P<0.05) in the model group. The pain threshold in the body-acupuncture group and the buccal acupuncture group at 0 and 1 h (P<0.05 or P<0.01) increased significantly, while the ß-EP and CCK-8 contents in the body-acupuncture group and the buccal acupuncture group were significantly higher than those in the model group (P<0.01 or P<0.05). Both ß-EP and CCK-8 contents in the buccal acupuncture group at 0 h were significantly higher than those in the body-acupuncture group (P<0.05).
 Conclusion: The analgesic effect of buccal acupuncture is superior to that of body-acupuncture. Both buccal acupuncture and body-acupuncture can effectively raise the pain threshold in acute arthritis rabbits, which is closely associated with their effects in the up-regulation of ß-EP and CCK-8 contents in cerebrospinal fluid.

The role of long non-coding RNA in Crohn's disease.

Emerging evidence has illuminated the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating immunological functions and autoimmune responses. In the context of Crohn's disease (CD), an array of novel lncRNAs has been identified in the plasma and intestinal tissues of afflicted individuals, suggesting a dualistic influence on the disease progression, either exacerbating or mitigating its course. Current research has demonstrated the involvement of lncRNAs in competitive endogenous RNA, the inflammation process, epithelial barrier function, gut microbiota imbalance, and epigenetic regulation. This review aims to encapsulate the current knowledge on the lncRNA contribution to CD and underscore potential avenues for future research. LncRNAs are increasingly recognized as significant biomarkers and potential therapeutic targets, holding a key position in the pathogenesis of CD. Furthermore, the unique attributes of circulating lncRNAs, such as minimal side effects, combinational therapy potential, and personalized medicine, render them as promising therapeutic tools for individual health management in CD.

Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway.

BACKGROUND: Ulcer colitis (UC) is a chronic, nonspecific, and noninfectious inflammatory bowel disease. Recently, Toll-like receptors (TLRs) have been found to be closely associated with clinical inflammatory diseases. Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging. Moreover, no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. AIM: To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. METHODS: This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021. The patients with UC were divided into two groups (control and experimental). The peripheral blood of the experimental and control groups were collected under aseptic conditions. The expression of TLR4 protein, NF-κB, IL-6, and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug. Linear correlation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17, and P < 0.05 was considered statistically significant. RESULTS: There were no significant differences in the patient characteristics between the control and experimental groups. The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group (P < 0.05). The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group (P < 0.05). The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17 (r = 0.823, P < 0.05). CONCLUSION: Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

Circ_0068481 Affects the Human Pulmonary Artery Smooth Muscle Cells' Progression by miR-361-3p/KLF5 Axis.

BACKGROUND: Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). In this work, we defined the precise part of circ_0068481 in PASMC proliferation and migration induced by hypoxia. We hypothesized that circ_0068481 enhanced hypoxia-induced PASMC proliferation, invasion, and migration through the microRNA (miR)-361-3p/Krüppel-like factor 5 (KLF5) pathway. METHODS: Human PASMCs (hPASMCs) were exposed to hypoxic (3% O2) conditions. Circ_0068481, miR-361-3p, and KLF5 levels were gauged by qRT-PCR and western blot. Cell viability, proliferation, invasion, and migration were detected by XTT, EdU incorporation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were performed to confirm the direct relationship between miR-361-3p and circ_0068481 or KLF5. RESULTS: Circ_0068481 expression was increased in the serum of PAH patients and hypoxia-induced hPASMCs. Downregulation of circ_0068481 attenuated hypoxia-induced promotion in hPASMC proliferation, invasion, and migration. Circ_0068481 directly targeted miR-361-3p, and miR-361-3p downregulation reversed the inhibitory effects of circ_0068481 silencing on hypoxia-induced hPASMC proliferation, invasion, and migration. KLF5 was a direct miR-361-3p target, and miR-361-3p upregulation mitigated hypoxia-induced hPASMC proliferation, invasion, and migration by inhibiting KLF5 expression. Moreover, circ_0068481-induced KLF5 expression by binding to miR-361-3p in hypoxic hPASMCs. CONCLUSIONS: Circ_0068481 knockdown ameliorated hypoxia-induced hPASMC proliferation, invasion, and migration at least in part through the miR-361-3p/KLF5 axis.

Chitosan-based oral nanoparticles as an efficient platform for kidney-targeted drug delivery in the treatment of renal fibrosis.

There is increasingly keen interest in developing orally delivered targeted drugs, especially for diseases that require long-term medication. Hence, we manufactured nanoparticles derived from methoxypolyethylene glycol-chitosan (PCS) to enhance the oral delivery and kidney-targeted distribution of salvianolic acid B (SalB), a naturally occurring renoprotective and anti-fibrotic compound, as a model drug for the treatment of renal fibrosis. Orally administered SalB-loaded PCS nanoparticles (SalB-PCS-NPs) maintained good stability in the gastrointestinal environment, improved mucus-penetrating capacity, and enhanced transmembrane transport through a Caco-2 cell monolayer. The relative oral bioavailability of SalB-PCS-NPs to free SalB and SalB-loaded chitosan nanoparticles (SalB-CS-NPs) was 367.0 % and 206.2 %, respectively. The structural integrity of SalB-PCS-NPs after crossing the intestinal barrier was also validated by Förster resonance energy transfer (FRET) in vitro and in vivo. Fluorescein isothiocyanate (FITC)-labeled SalB-PCS-NPs showed higher kidney accumulation than free FITC and FITC-labeled SalB-CS-NPs (4.6-fold and 2.1-fold, respectively). Significant improvements in kidney function, extracellular matrix accumulation, and pathological changes were observed in a unilateral ureter obstruction mouse model of renal fibrosis after once daily oral treatment with SalB-PCS-NPs for 14 days. Thus, oral administration of SalB-PCS-NPs represents a promising new strategy for kidney-targeted drug delivery.

Twist piezoelectricity: giant electromechanical coupling in magic-angle twisted bilayer LiNbO3.

Twisted a pair of stacked two-dimensional materials exhibit many exotic electronic and photonic properties, leading to the emergence of flat-band superconductivity, moiré engineering and topological polaritons. These remarkable discoveries make twistronics the focus point of tremendous interest, but mostly limited to the concept of electrons, phonons or photons. Here, we present twist piezoelectricity as a fascinating paradigm to modulate polarization and electromechanical coupling by twisting precisely the stacked lithium niobate slabs due to the interlayer coupling effect. Particularly, the inversed and twisted bilayer lithium niobate is constructed to overcome the intrinsic mutual limitation of single crystals and giant effective electromechanical coupling coefficient k t 2 is unveiled at magic angle of 11 1 ∘ , reaching 85.5%. Theoretical analysis based on mutual energy integrals shows well agreements with numerical and experimental results. Our work opens new venues to flexibly control multi-physics with magic angle, stimulating progress in wideband acoustic-electric, and acoustic-optic components, which has great potential in wireless communication, timing, sensing, and hybrid integrated photonics.

Gut microbiota dysbiosis contributes to α-synuclein-related pathology associated with C/EBPß/AEP signaling activation in a mouse model of Parkinson's disease.

JOURNAL/nrgr/04.03/01300535-202409000-00042/figure1/v/2024-01-16T170235Z/r/image-tiff Parkinson's disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction. Gastrointestinal dysfunction can precede the onset of motor symptoms by several years. Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson's disease, whether it plays a causal role in motor dysfunction, and the mechanism underlying this potential effect, remain unknown. CCAAT/enhancer binding protein ß/asparagine endopeptidase (C/EBPß/AEP) signaling, activated by bacterial endotoxin, can promote α-synuclein transcription, thereby contributing to Parkinson's disease pathology. In this study, we aimed to investigate the role of the gut microbiota in C/EBPß/AEP signaling, α-synuclein-related pathology, and motor symptoms using a rotenone-induced mouse model of Parkinson's disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation. We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier, as well as activation of the C/EBP/AEP pathway, α-synuclein aggregation, and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits. However, treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics. Importantly, we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits, intestinal inflammation, and endotoxemia. Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits, intestinal inflammation, endotoxemia, and intestinal barrier impairment. These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits, C/EBPß/AEP signaling activation, and α-synuclein-related pathology in a rotenone-induced mouse model of Parkinson's disease. Additionally, our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson's disease.

Evaluation of the mechanical properties and clinical application of nickel-titanium shape memory alloy anal fistula clip.

Objective: The study investigates the mechanical properties of a nickel-titanium shape memory alloy anal fistula clip (NiTi-AFC), studies the surgical method of treating anal fistula, and evaluates its clinical efficacy. Methods: The anal fistula clip was formed in nickel-titanium alloy with a titanium content of 50.0%-51.8%. The mechanical properties and chemical properties were tested. A total of 31 patients with anal fistula were enrolled between 1 January 2020 and 1 January 2023. All patients underwent internal orifice closure surgery using NiTi-AFC, and anorectal magnetic resonance or ultrasound was performed before surgery and 6 months after surgery for diagnosis and evaluation. Fistula cure rates, length of stay, perianal pain, and Wexner incontinence scores were retrospectively compared between patients treated with NiTi-AFC and patients treated with other surgical methods. Result: NiTi-AFC has a density of 6.44-6.50 g·cm-3, with a shape-restoring force of 63.8 N. The corrosion rate of NiTi-AFC in 0.05% hydrochloric acid solution at atmospheric pressure and 20°C is approximately 6.8 × 10-5 g·(m·h)-1. A total of 31 patients (male/female: 19/12, age: 43.7 ± 17.8 years) were included. Among them, 22.6% (7) had multiple anal fistula, 16.1% (5) had high anal fistula, and 48.3% (15) had perianal fistula Crohn's disease. In total, 12.9% (4/31) did not achieve primary healing, underwent fistula resection, and eventually recovered. A retrospective analysis showed that the fistula healing rate, length of stay, and anal pain of NiTi-AFC treatment were similar to those of other traditional surgeries, but the Wexner incontinence score was significantly lower. Conclusion: NiTi-AFC has shape memory properties, corrosion resistance, superelastic effect, and surface cell adhesion. It is applied to internal orifice closure surgery of anal fistula, with good therapeutic effect, and can protect the anal function.