Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.

BACKGROUND: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear. AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC). METHODS: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1ß, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-ß, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing. RESULTS: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-ß, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1ß, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora. CONCLUSION: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.

Luminescent metal nanoclusters and their application in bioimaging.

Owing to their unique optical properties and atomically precise structures, metal nanoclusters (MNCs) constitute a new generation of optical probe materials. This mini-review provides a brief overview of luminescence mechanisms and modulation methods of luminescent metal nanoclusters in recent years. Based on these photophysical phenomena, the applications of cluster-based optical probes in optical bioimaging and related sensing, disease diagnosis, and treatment are summarized. Some challenges are also listed at the end.

Tetraalkynylporphyrin-mediated covalent assembly of gold nanoclusters for targeted tumor fluorescence imaging and enhanced photodynamic therapy.

A covalent assembly strategy was developed to construct a gold nanocluster-based nano-assembly (AuNCNA) in a controllable manner, using Au8 nanocluster as node and 5,10,15,20-tetra(4-alkynylphenyl)porphine (TEPP) as ligand. Subsequently, the tripeptide arginine glycine aspartic acid (RGD) peptide is further modified via clicking reaction to build a multi-functional nanoplatform (AuNCNA@RGD) that can integrate the targeted fluorescence imaging and efficient photodynamic therapy (PDT). The strong interregulation of Au8 nanocluster and TEPP results in AuNCNA@RGD exhibiting three distinct advantages: (i) TEPP plays an important role in stabilizing the Au8 nanocluster and keeping the active site fixed within the framework, thereby enhancing stability of Au8 nanocluster; (ii) Au8 nanocluster possess adjustable energy level, which can accelerate the transfer of photogenerated charge and prevent the recombination of electrons and holes, thus improving the photosensitivity of TEPP for PDT; (iii) AuNCNA exhibits bright fluorescence emission that facilitates RGD-assisted targeted tumor imaging. This work expands the construction method of AuNC assembly, and this assembly method is versatile and can flexibly transform different organic ligands to construct various AuNC-based functional nanomaterials.

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Accurate assessment of material and energy exchange between land and atmosphere is essential for water resources management and sustainable development of agriculture. To understand the characteristics of energy distribution and the dynamic change process of water and heat fluxes within the maize farmland ecosystem in the old course of Yellow River and their response to meteorological factors, we utilized the eddy covariance measurements and the full-element automatic weather station to continuously observe energy fluxes and conventional meteorological elements of summer maize farmland in the old course of Yellow River during 2019-2020. We analyzed the variation of energy fluxes and the effects of environmental factors, such as temperature, precipitation, and wind speed. Additionally, we calculated the energy closure rate and the proportion of energy distribution during the growth stage. The results showed that the peaks of net radiation, sensible heat flux, and latent heat flux occurred between 11:00 and 14:00, and the peak of soil heat flux occurred between 14:00 and 15:00. In terms of energy distribution, energy consumption of summer maize farmland during the whole growth period was dominated by latent heat flux and sensible heat flux. Energy was mainly consumed by sensible heat flux at sowing-emergence stage, accounting for 37.1% of net radiation, respectively. Energy in the rest of growth stages was dominated by latent heat flux. The energy closure rate during the whole growth period was better, with a coefficient of determination of 0.83, and the closure rate was higher in day and lower at night. Precipitation affected latent heat flux and sensible heat flux, and latent heat flux was more sensitive to precipitation. The increase of latent heat flux after rainfall was lower in late growth stage than in early growth stage. During the whole growth period of summer maize, solar radiation was the most significant meteorological factor affecting both sensible heat flux and latent heat flux, followed by vapor pressure deficit. The contribution of temperature and vapor pressure deficit to latent heat flux was significantly higher than sensible heat flux, while the relative contribution of wind speed, relative humidity, and solar radiation to latent heat flux was lower than sensible heat flux. Leaf area index and fractional vegetation cover had a significant positive correlation with latent heat flux and a significant negative correlation with sensible heat flux. Our results could deepen the understanding of water and heat transfer law of summer maize farmland in the old course of Yellow River, providing a theoretical basis for efficient water use of crops.

Helically twisted nonlinear photonic crystals.

Nonlinear photonic crystals with a helical structure in the second-order nonlinear coefficient (χ(2)) are fabricated using infrared femtosecond laser poling in ferroelectric Sr0.61Ba0.39Nb2O6 crystals. The quasi-orbital angular momentum of the helical χ(2) structure can be imprinted on the interacting photons during nonlinear optical processes, allowing the topological charge of the generated photons at new frequencies to be controlled. Here we study the case of a double-helix nonlinear photonic structure for the generation of a second-harmonic vortex beam from a Gaussian pump beam without phase singularity. The conservation law for orbital angular momentum in the second-harmonic process is also verified, with the topological charge of the pump photons being fully compensated by the double-helix structure. The flexible control of light carrying orbital angular momentum (OAM) at new frequencies will find important applications in both classical and quantum photonics, such as nonlinear wavefront shaping and multidimensional entanglement of photons.

Effects of Different Test Positions on Quantitative Muscle Strength of Wrist and Finger Flexor Muscle Groups and Its Standardization.

OBJECTIVES: To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group. METHODS: Forty healthy subjects (12 males and 28 females) were recruited. A portable digital quantitative muscle strength tester, Micro FET2TM, was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension, 0° neutral, and 30° flexion, respectively. Palmar abduction strength of the thumb was measured at 30° and 60°, respectively. Ten subjects were randomly selected from the 40 subjects, and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days. RESULTS: Except for the fact that in males, there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position, the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics：30° of wrist extension > neutral 0° position > 30° of flexion, and the PAST was 30°>60°; The flexor muscle strength of all the subjects was thumb > index finger > middle finger > ring finger > little finger; All muscle strength values of male were greater than those of female, and the difference was statistically significant (P<0.05); There was no significant difference between the left and right side muscle strength values of all subjects (P>0.05). The reliability of muscle strength values measured at different times in 10 subjects was good. CONCLUSIONS: The quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position, and a standardized and uniformed test position should be adopted in the actual identification. Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing. The 30° extension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint. The 30° position can be used as the best standardized test position for PAST.

Ac4C modification of lncRNA SIMALR promotes nasopharyngeal carcinoma progression through activating eEF1A2 to facilitate ITGB4/ITGA6 translation.

The dysregulation of long non-coding RNAs (lncRNAs) are involved in regulating tumor progression in multiple manner. However, little is known about whether lncRNA is involved in the translation regulation of proteins. Here, we identified that the suppressor of inflammatory macrophage apoptosis lncRNA (SIMALR) was highly expressed in nasopharyngeal carcinoma (NPC) tissues by analyzing the lncRNA microarray. Clinically, the high expression of SIMALR served as an independent predictor for inferior prognosis in NPC patients. SIMALR functioned as an oncogenic lncRNA that promoted the proliferation and metastasis of NPC cells in vitro and in vivo. Mechanistically, SIMALR served as a critical accelerator of protein synthesis by binding to eEF1A2 (eukaryotic translation elongation factor 1 alpha 2), one of the most crucial regulators in the translation machinery of the eukaryotic cells, and enhancing its endogenous GTPase activity. Furthermore, SIMALR mediated the activation of eEF1A2 phosphorylation to accelerate the translation of ITGB4/ITGA6, ultimately promoting the malignant phenotype of NPC cells. In addition, N-acetyltransferase 10 (NAT10) enhanced the stability of SIMALR and caused its overexpression in NPC through the N4-acetylcytidine (ac4C) modification. In sum, our results illustrate SIMALR functions as an accelerator for protein translation and highlight the oncogenic role of NAT10-SIMALR-eEF1A2-ITGB4/6 axis in NPC.

DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.

Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.

PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma.

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system.

Enhancing antioxidant levels and mitochondrial function in porcine oocyte maturation and embryonic development through notoginsenoside R1 supplementation.

This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.

Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors.

Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary. This study investigated the potential of using a clinically available ultrasound system and phase 2-proven microbubbles to relieve tumor hypoxia and enhance the efficacy of chemotherapy and immunotherapy in a murine PDAC model. This approach enables early PDAC detection and blood-flow-sensitive Power-Doppler sonoporation in combination with chemotherapy. It significantly extended treated mice's median survival compared to chemotherapy alone. Mechanistically, this combination therapy enhanced tumor perfusion and substantially reduced tumor hypoxia (77% and 67%, 1- and 3-days post-treatment). Additionally, cluster of differentiation 8 (CD8) T-cell infiltration increased four-fold afterward. The combined treatment demonstrated a strengthening of the anti-programmed death-ligand 1(αPDL1) therapy against PDAC. Our study illustrates the feasibility of using a clinically available ultrasound system with NH-002 microbubbles for early tumor detection, alleviating hypoxic TME, and improving chemotherapy and immunotherapy. It suggests the development of an adjuvant theragnostic protocol incorporating Power-Doppler sonoporation for pancreatic tumor treatment.

LncRNA DYNLRB2-AS1 promotes gemcitabine resistance of nasopharyngeal carcinoma by inhibiting the ubiquitination degradation of DHX9 protein.

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

The function of the ATG8 in the cilia and cortical microtubule maintenance of Euplotes amieti.

Autophagy regulates the formation of primary cilia, which in turn affects autophagy. The relationship between autophagy and cilia is known to be bidirectional although the specific mechanisms involved have yet to be elucidated. In this study, we found for the first time that ATG8 protein localizes in the basal body of the dorsal kineties and the base of the ventral cirri in Euplotes amieti. ATG8 protein maintains the structural integrity of cilia and plays a role in the construction of the cortical ciliature and microtubule cytoskeleton associated with cilia. ATG8 gene interference leads to the degradation of IFT88, the transport protein in cilia, thus inhibiting the generation of cilia, and affecting the swing of cilia. This influences the swimming speed and cilia pattern, leading to death in Euplotes amieti.

Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.

Neurobrucellosis: laboratory features, clinical characteristics, antibiotic treatment, and clinical outcomes of 21 patients.

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.

Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms.

Efferocytosis is defined as the highly effective phagocytic removal of apoptotic cells (ACs) by professional or non-professional phagocytes. Tissue-resident professional phagocytes ("efferocytes"), such as macrophages, have high phagocytic capacity and are crucial to resolve inflammation and aid in homeostasis. Recently, numerous exciting discoveries have revealed divergent (and even diametrically opposite) findings regarding metabolic immune reprogramming associated with efferocytosis by macrophages. In this review, we highlight the key metabolites involved in the three phases of efferocytosis and immune reprogramming of macrophages under physiological and pathological conditions. The next decade is expected to yield further breakthroughs in the regulatory pathways and molecular mechanisms connecting immunological outcomes to metabolic cues as well as avenues for "personalized" therapeutic intervention.

Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Carbohydrate Mouth Rinses before Exercise Improve Performance of Romanian Deadlift Exercise: A Randomized Crossover Study.

(1) Background: This study compared the effects of mouth rinsing with a carbohydrate trial (CMR) and a placebo trial (PL) on concentric and eccentric contraction strength in multi-joint resistance exercise performance. (2) Methods: Twenty healthy adult men (age: 22.4 ± 3.7 years, body mass index: 26 ± 3.8, peak power: 378.3 ± 138.7 W) were recruited in this study. Participants were employed in a double-blind, randomized crossover design to divide participants into carbohydrate mouth rinsing trial (CMR) and placebo trial (PL). After warming up, participants used 6.6% maltodextrin (CMR) or mineral water (PL) to rinse their mouth for 20 s. Next, the participants underwent tests of maximum inertial Romanian deadlift resistance exercise comprising five sets of six reps, with 3 min rests between sets. After deducting the first repetition of each set, the mean values from the five sets were analyzed. (3) Results: The concentric peak power of the CMR trial was significantly higher than that of the PL trial (p = 0.001, Cohen's d = 0.46), the eccentric peak power of the CMR trial was significantly higher than that of the PL trial (p = 0.008, Cohen's d = 0.56), and the total work of the CMR trial was significantly higher than that of PL trial (p = 0.002, Cohen's d = 0.51). (4) Conclusions: These findings demonstrate that mouth rinsing with carbohydrates before exercise can improve concentric and eccentric contraction strength in multi-joint resistance exercise performance.

Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes: A cross-sectional study.

BACKGROUND: Dietary fiber (DF) intake may have a protective effect against type 2 diabetes (T2D); however, its relationship with diabetic kidney disease (DKD) remains unclear. AIM: To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018. DF intake was assessed through 24-h dietary recall interviews, and DKD diagnosis in individuals with T2D was based on predefined criteria, including albuminuria, impaired glomerular filtration rate, or a combination of both. Logistic regression analysis was used to assess the association between DF intake and DKD, and comprehensive subgroup and sensitivity analyses were performed. RESULTS: Among the 6032 participants, 38.4% had DKD. With lower DF intake-T1 (≤ 6.4 g/1000 kcal/day)-as a reference, the adjusted odds ratio for DF and DKD for levels T2 (6.5-10.0 g/1000 kcal/day) and T3 (≥ 10.1 g/1000 kcal/day) were 0.97 (95%CI: 0.84-1.12, P = 0.674) and 0.79 (95%CI: 0.68-0.92, P = 0.002), respectively. The subgroup analysis yielded consistent results across various demographic and health-related subgroups, with no statistically significant interactions (all P > 0.05). CONCLUSION: In United States adults with T2D, increased DF intake may be related to reduced DKD incidence. Further research is required to confirm these findings.

The CRISPR-Cas13a Gemini System for noncontiguous target RNA activation.

Simultaneous multi-target detection and multi-site gene editing are two key factors restricting the development of disease diagnostic and treatment technologies. Despite numerous explorations on the source, classification, functional features, crystal structure, applications and engineering of CRISPR-Cas13a, all reports use the contiguous target RNA activation paradigm that only enables single-target detection in vitro and one-site gene editing in vivo. Here we propose a noncontiguous target RNA activation paradigm of Cas13a and establish a CRISPR-Cas13a Gemini System composed of two Cas13a:crRNA binary complexes, which can provide rapid, simultaneous, highly specific and sensitive detection of two RNAs in a single readout, as well as parallel dual transgene knockdown. CRISPR-Cas13a Gemini System are demonstrated in the detection of two miRNAs (miR-155 and miR-375) for breast cancer diagnosis and two small RNAs (EBER-1 and EBER-2) for Epstein-Barr virus diagnosis using multiple diagnostic platforms, including fluorescence and colorimetric-based lateral flow systems. We also show that CRISPR-Cas13a Gemini System can knockdown two foreign genes (EGFP and mCherry transcripts) in mammalian cells simultaneously. These findings suggest the potential of highly effective and simultaneous detection of multiple biomarkers and gene editing of multiple sites.