Neuronal population activity in the olivocerebellum encodes the frequency of essential tremor in mice and patients.

Essential tremor (ET) is the most prevalent movement disorder, characterized primarily by action tremor, an involuntary rhythmic movement with a specific frequency. However, the neuronal mechanism underlying the coding of tremor frequency remains unexplored. Here, we used in vivo electrophysiology, optogenetics, and simultaneous motion tracking in the Grid2dupE3 mouse model to investigate whether and how neuronal activity in the olivocerebellum determines the frequency of essential tremor. We report that tremor frequency was encoded by the temporal coherence of population neuronal firing within the olivocerebellums of these mice, leading to frequency-dependent cerebellar oscillations and tremors. This mechanism was precise and generalizable, enabling us to use optogenetic stimulation of the deep cerebellar nuclei to induce frequency-specific tremors in wild-type mice or alter tremor frequencies in tremor mice. In patients with ET, we showed that deep brain stimulation of the thalamus suppressed tremor symptoms but did not eliminate cerebellar oscillations measured by electroencephalgraphy, indicating that tremor-related oscillations in the cerebellum do not require the reciprocal interactions with the thalamus. Frequency-disrupting transcranial alternating current stimulation of the cerebellum could suppress tremor amplitudes, confirming the frequency modulatory role of the cerebellum in patients with ET. These findings offer a neurodynamic basis for the frequency-dependent stimulation of the cerebellum to treat essential tremor.

PPARγ Antagonists Exhibit Antitumor Effects by Regulating Ferroptosis and Disulfidptosis.

Oral squamous cell carcinoma (OSCC) stands as a prevalent subtype of head and neck squamous cell carcinoma, leading to disease recurrence and low survival rates. PPARγ, a ligand-dependent nuclear transcription factor, holds significance in tumor development. However, the role of PPARγ in the development of OSCC has not been fully elucidated. Through transcriptome sequencing analysis, we discovered a notable enrichment of ferroptosis-related molecules upon treatment with PPARγ antagonist. We subsequently confirmed the occurrence of ferroptosis through transmission electron microscopy, iron detection, etc. Notably, ferroptosis inhibitors could not completely rescue the cell death caused by PPARγ inhibitors, and the rescue effect was the greatest when disulfidptosis and ferroptosis inhibitors coexisted. We confirmed that the disulfidptosis phenotype indeed existed. Mechanistically, through qPCR and Western blotting, we observed that the inhibition of PPARγ resulted in the upregulation of heme oxygenase 1 (HMOX1), thereby promoting ferroptosis, while solute carrier family 7 member 11 (SLC7A11) was also upregulated to promote disulfidptosis in OSCC. Finally, a flow cytometry analysis of flight and multiplex immunohistochemical staining was used to characterize the immune status of PPARγ antagonist-treated OSCC tissues in a mouse tongue orthotopic transplantation tumor model, and the results showed that the inhibition of PPARγ led to ferroptosis and disulfidptosis, promoted the aggregation of cDCs and CD8+ T cells, and inhibited the progression of OSCC. Overall, our findings reveal that PPARγ plays a key role in regulating cell death in OSCC and that targeting PPARγ may be a potential therapeutic approach for OSCC.

Tauroursodeoxycholic acid ameliorates renal injury induced by COL4A3 mutation.

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed that the MyD88/p38 MAPK pathway plays key roles in mediating subsequent inflammation and apoptosis signaling activation. Treatment with tauroursodeoxycholic acid, a chemical chaperone drug that functions as an endoplasmic reticulum stress inhibitor, effectively suppressed endoplasmic reticulum stress, promoted secretion of the α3 chains, and inhibited the activation of the MyD88/p38 MAPK pathway. Tauroursodeoxycholic acid treatment significantly improved kidney function in vivo. These results partly clarified the pathogenesis of kidney injuries associated with Alport syndrome, especially in glomeruli, and suggested that tauroursodeoxycholic acid might be useful for the early clinical treatment of Alport syndrome.

PA28γ induces dendritic cell maturation and activates T-cell immune responses in oral lichen planus.

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune-related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear. Here, we demonstrated that PA28γ is overexpressed in epithelial cells and inflammatory cells of OLP tissues but has no significant relationship with OLP subtypes. Functionally, keratinocytes with high PA28γ expression could induce dendritic cell (DC) maturation and promote the T-cell differentiation into Th1 cells in response to the immune response. In addition, we found that a high level of PA28γ expression is associated with high numbers of infiltrating mature DCs and activated T-cells in OLP tissues. Mechanistically, keratinocytes with high PA28γ expression could promote the secretion of C-C motif chemokine (CCL)5, blocking CCL5 or/and its receptor CD44 could inhibit the induction of T-cell differentiation by keratinocytes with high PA28γ expression. In conclusion, we reveal that keratinocytes with high expression of PA28γ in OLP can induce DC maturation and promote T-cell differentiation through the CCL5-CD44 pathway, providing previously unidentified mechanistic insights into the mechanism of inflammatory progression in OLP.

Effects of Helicobacter pylori and Moluodan on the Wnt/ß-catenin signaling pathway in mice with precancerous gastric cancer lesions.

BACKGROUND: Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/ß-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. AIM: To explore the effects of H. pylori and Moluodan on the Wnt/ß-Catenin signaling pathway and precancerous lesions of GC (PLGC). METHODS: Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. RESULTS: Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. CONCLUSION: H. pylori can activate the Wnt/ß-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/ß-catenin signaling pathway, thereby decreasing the progression of PLGC.

Live and Heat-Inactivated Streptococcus thermophilus MN-ZLW-002 Mediate the Gut-Brain Axis, Alleviating Cognitive Dysfunction in APP/PS1 Mice.

Research on regulating brain functions with probiotics and postbiotics through the gut-brain axis is attracting attention, offering the possibility of adjuvant therapy for Alzheimer's disease (AD). Three-month-old male APP/PS1 mice were gavaged with live and heat-inactivated S. thermophilus MN-002 for three months. This study demonstrated that live and heat-inactivated S. thermophilus MN-002 improved cognitive dysfunctions in APP/PS1 mice, especially in spatial memory. However, the main effects of live S. thermophilus MN-002 directly altered the intestinal microbiota composition and increased serum IL-1ß and IL-6. Heat-inactivated S. thermophilus MN-002 increased colonic propionic acid levels and enhanced the hippocampus's antioxidant capacity. Furthermore, the changes were more obvious in the high-dose group, such as astrogliosis in the hippocampus. These results indicate that different forms and doses of the same strain, S. thermophilus MN-002, can partly improve cognitive functions in AD model mice via the gut-brain axis.

Cyano-Functionalized Pyrazine: A Structurally Simple and Easily Accessible Electron-Deficient Building Block for n-Type Organic Thermoelectric Polymers.

Developing low-cost and high-performance n-type polymer semiconductors is essential to accelerate the application of organic thermoelectrics (OTEs). To achieve this objective, it is critical to design strong electron-deficient building blocks with simple structure and easy synthesis, which are essential for the development of n-type polymer semiconductors. Herein, we synthesized two cyano-functionalized highly electron-deficient building blocks, namely 3,6-dibromopyrazine-2-carbonitrile (CNPz) and 3,6-Dibromopyrazine-2,5-dicarbonitrile (DCNPz), which feature simple structures and facile synthesis. CNPz and DCNPz can be obtained via only one-step reaction and three-step reactions from cheap raw materials, respectively. Based on CNPz and DCNPz, two acceptor-acceptor (A-A) polymers, P(DPP-CNPz) and P(DPP-DCNPz) are successfully developed, featuring deep-positioned lowest unoccupied molecular orbital (LUMO) energy levels, which are beneficial to n-type organic thin-film transistors (OTFTs) and OTEs performance. An optimal unipolar electron mobility of 0.85 and 1.85 cm2 V-1 s-1 is obtained for P(DPP-CNPz) and P(DPP-DCNPz), respectively. When doped with N-DMBI, P(DPP-CNPz) and P(DPP-DCNPz) show high n-type electrical conductivities/power factors of 25.3 S cm-1 /41.4 µW m-1 K-2 , and 33.9 S cm-1 /30.4 µW m-1 K-2 , respectively. Hence, the cyano-functionalized pyrazine CNPz and DCNPz represent a new class of structurally simple, low-cost and readily accessible electron-deficient building block for constructing n-type polymer semiconductors.

Synthesis of lipophilic antioxidant tyrosol laurate using imidazolium ionic liquid [Bmim]HSO4 as a catalyst.

Tyrosol is a natural phenolic compound with potent antioxidant properties in the field of food manufacturing. However, the low lipophilicity of tyrosol limited its application. Therefore, the construction of tyrosol laurate (Tyr-L) could effectively overcome the limitations of tyrosol. In this work, four ionic liquids (ILs) were applied for TYr-L preparation. Among them, the 1-butyl-3-methylimidazolium hydrogen sulfate ([Bmim]HSO4) showed the best catalytic performance. The maximum TYr-L yield was achieved (94.24 ± 1.23 %) under the optimal conditions (reaction temperature 119 °C, substrate ratio 1:6.7, IL dosage 9.2 %, and reaction time 12 h). The kinetic and thermodynamic parameters were also evaluated and it was found that Ea, ΔH, ΔS, and ΔG were 80.81 kJ·mol-1, 77.63 kJ·mol-1, -82.08 J·(mol·K)-1, and 109.89 kJ·mol-1, respectively. The acidic [Bmim]HSO4 demonstrated excellent reusability and stability, even after 6 cycles. Furthermore, TYr-L showed superior ABTS radical scavenging ability, which could be further applied in various industrial processes.

Characterization of the Disinfectant Resistance Genes qacEΔ1 and cepA in Carbapenem-Resistant Klebsiella pneumoniae Isolates.

The emergence and wide global spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are of great concern. This multicenter study aimed to investigate the molecular characteristics of CRKP isolates from inpatients in Wuhan, China. From June 2018 to March 2019, 74 nonduplicated CRKP clinical isolates were collected from six hospitals in Wuhan. We determined the minimum inhibitory concentrations of 18 antibiotics and used real-time polymerase chain reaction to detect the presence of disinfectant resistance genes qacEΔ1 and cepA. Pulsed-field gel electrophoresis was conducted to assess the genetic relatedness of isolates. Among the 74 CRKP isolates, the rates of resistance to carbapenems were high: 93.2% to ertapenem, 90.5% to imipenem, and 87.8% to meropenem. All isolates were resistant to at least one carbapenem antibiotic. Of the 74 isolates, 64.9% (48/74) were positive for qacEΔ1 and 93.2% (69/74) for cepA. QacEΔ1 and cepA were detected concomitantly in 46 isolates (62.2%), whereas only 4.1% (3/74) had no disinfectant resistance genes. Pulsed-field gel electrophoresis analysis clustered the 46 CRKP strains co-producing qacEΔ1 and cepA into 15 different clonal clusters (Types A to O). The most common clonal clusters were Type C (41.3%), Type E (13.0%), and Type J (8.7%). The study showed high rates of resistance to most antibiotics and high frequency of qacEΔ1 and cepA in CRKP isolates. Specific clonal dissemination of CRKP was detected within the same hospital or between different hospitals. Therefore, medical institutions should choose and use disinfectants correctly to prevent the spread of CRKP.

High-Performance n-Type Polymeric Mixed Ionic-Electronic Conductors: The Impacts of Halogen Functionalization.

Developing high-performance n-type polymer mixed ionic-electronic conductors (PMIECs) is a grand challenge, which largely determines their applications in vaious organic electronic devices, such as organic electrochemical transistors (OECTs) and organic thermoelectrics (OTEs). Herein, two halogen-functionalized PMIECs f-BTI2g-TVTF and f-BTI2g-TVTCl built from fused bithiophene imide dimer (f-BTI2) as the acceptor unit and halogenated thienylene-vinylene-thienylene (TVT) as the donor co-unit are reported. Compared to the control polymer f-BTI2g-TVT, the fluorinated f-BTI2g-TVTF shows lower-positioned lowest unoccupied molecular orbital (LUMO), improved charge transport property, and greater ion uptake capacity. Consequently, f-BTI2g-TVTF delivers a state-of-the-art µC* of 90.2 F cm-1 V-1 s-1 with a remarkable electron mobility of 0.41 cm2 V-1 s-1 in OECTs and an excellent power factor of 64.2 µW m-1 K-2 in OTEs. An OECT-based inverter amplifier is further demonstrated with voltage gain up to 148 V V-1 , which is among the highest values for OECT inverters. Such results shed light on the impacts of halogen atoms on developing high-performing n-type PMIECs.

Selenophene Substitution Enabled High-Performance n-Type Polymeric Mixed Ionic-Electronic Conductors for Organic Electrochemical Transistors and Glucose Sensors.

High-performance n-type polymeric mixed ionic-electronic conductors (PMIECs) are essential for realizing organic electrochemical transistors (OECTs)-based low-power complementary circuits and biosensors, but their development still remains a great challenge. Herein, by devising two novel n-type polymers (f-BTI2g-SVSCN and f-BSeI2g-SVSCN) containing varying selenophene contents together with their thiophene-based counterpart as the control, it is demonstrated that gradually increasing selenophene loading in polymer backbones can simultaneously yield lowered lowest unoccupied molecular orbital levels, boosted charge-transport properties, and improved ion-uptake capabilities. Therefore, a remarkable volumetric capacitance (C*) of 387.2 F cm-3 and a state-of-the-art OECT electron mobility (µe,OECT ) of 0.48 cm2 V-1 s-1 are synchronously achieved for f-BSeI2g-SVSCN having the highest selenophene content, yielding an unprecedented geometry-normalized transconductance (gm,norm ) of 71.4 S cm-1 and record figure of merit (µC*) value of 191.2 F cm-1 V-1 s-1 for n-type OECTs. Thanks to such excellent performance of f-BSeI2g-SVSCN-based OECTs, a glucose sensor with a remarkably low detection limit of 10 nMm and decent selectivity is further implemented, demonstrating the power of selenophene substitution strategy in enabling high-performance n-type PMIECs for biosensing applications.

Multi-Selenophene Incorporated Thiazole Imide-Based n-Type Polymers for High-Performance Organic Thermoelectrics.

Developing polymers with high electrical conductivity (σ) after n-doping is a great challenge for the advance of the field of organic thermoelectrics (OTEs). Herein, we report a series of thiazole imide-based n-type polymers by gradually increasing selenophene content in polymeric backbone. Thanks to the strong intramolecular noncovalent N⋅⋅⋅S interaction and enhanced intermolecular Se⋅⋅⋅Se interaction, with the increase of selenophene content, the polymers show gradually lowered LUMOs, more planar backbone, and improved film crystallinity versus the selenophene-free analogue. Consequently, polymer PDTzSI-Se with the highest selenophene content achieves a champion σ of 164.0 S cm-1 and a power factor of 49.0 µW m-1 K-2 in the series when applied in OTEs after n-doping. The σ value is the highest one for n-type donor-acceptor OTE materials reported to date. Our work indicates that selenophene substitution is a powerful strategy for developing high-performance n-type OTE materials and selenophene incorporated thiazole imides offer an excellent platform in enabling n-type polymers with high backbone coplanarity, deep-lying LUMO and enhanced mobility/conductivity.

Isomerized Green Solid Additive Engineering for Thermally Stable and Eco-Friendly All-Polymer Solar Cells with Approaching 19% Efficiency.

Laboratory-scale all-polymer solar cells (all-PSCs) have exhibited remarkable power conversion efficiencies (PCEs) exceeding 19%. However, the utilization of hazardous solvents and nonvolatile liquid additives poses challenges for eco-friendly commercialization, resulting in the trade-off between device efficiency and operation stability. Herein, an innovative approach based on isomerized solid additive engineering is proposed, employing volatile dithienothiophene (DTT) isomers to modulate intermolecular interactions and facilitate molecular stacking within the photoactive layers. Through elucidating the underlying principles of the DTT-induced polymer assembly on molecular level, a PCE of 18.72% is achieved for devices processed with environmentally benign solvents, ranking it among the highest record values for eco-friendly all-PSCs. Significantly, such superiorities of the DTT-isomerized strategy afford excellent compatibility with large-area blade-coating techniques, offering a promising pathway for industrial-scale manufacturing of all-PSCs. Moreover, these devices demonstrate enhanced thermal stability with a promising extrapolated T80 lifetime of 14 000 h, further bolstering their potential for sustainable technological advancement.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

BACKGROUND: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. RESULTS: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. CONCLUSION: This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

A Frequency-Dependent Dynamic Electric-Mechanical Network for Thin-Wafer Piezoelectric Transducers Polarized in the Thickness Direction: Physical Model and Experimental Confirmation.

This paper is concerned with electric-acoustic/acoustic-electric conversions of thin-wafer piezoelectric transducers polarized in the thickness direction. By introducing two mechanical components with frequency-dependent values, i.e., radiation resistance and radiation mass, into the equivalent circuit of the thin-wafer piezoelectric transducer, we established a frequency-dependent dynamic mechanic-electric equivalent network with four terminals for an arbitrary given frequency, an enhancement from the conventional circuit networks. We derived the analytic expressions of its electric-acoustic and acoustic-electric conversion impulse responses using the four-terminal equivalent circuit to replace the traditional six-terminal equivalent circuit for a thin-wafer transducer with harmonic vibrational motion. For multifrequency electrical/acoustic signals acting on the transducer, we established parallel electric-acoustic/acoustic-electric conversion transmission networks. These two transmission network models have simple structures and clear physical and mathematical descriptions of thin-wafer transducers for electric-acoustic/acoustic-electric conversion when excited by a multifrequency electric/acoustic signal wavelet. The calculated results showed that the transducer's center frequency shift relates to its mechanical load and vibration state. The method reported in this paper can be applied to conventional-sized and small-sized piezoelectric transducers with universal applicability.

Rapid, sensitive, and highly specific detection of monkeypox virus by CRISPR-based diagnostic platform.

Background: Monkeypox (MPX), caused by the Monkeypox virus (MPXV), has incurred global attention since it broke out in many countries in recent times, which highlights the need for rapid and reliable diagnosis of MPXV infection. Methods: We combined recombinase polymerase amplification (RPA) with CRISPR/Cas12a-based detection to devise a diagnostic test for detection of MPXV and differentiation of its two clades [Central Africa clade (MPXV-CA) and West Africa clade (MPXV-WA)], and called it MPXV-RCC. The sensitivity, specificity and practicability of this method have been analyzed. Results: The optimal conditions of MPXV-RCC assay include two RPA reactions at 38°C for 25 min and a CRISPR/Cas12a-gRNA detection at 37°C for 10 min. The results of MPXV-RCC assay were indicated by a real-time fluorescence analysis software. Thus, the whole detection process, including rapid template preparation (20 min), RPA reaction (25 min) and CRISPR-based detection (10 min), could be finished within 1 hour. The sensitivity of MPXV-RCC for MPXV-CA and MPXV-WA detection was down to 5~10 copies of recombination plasmids and pseudovirus per reaction. Particularly, MPXV-RCC assay could clearly differentiate MPXV-CA from MPXV-WA, and had no cross-reactivity with other pathogens. In addition, the feasibility of MPXV-RCC assay was further validated by using spiked clinical samples. Conclusion: The MPXV-RCC assay developed here is a promising tool for quick and reliable diagnosis of MPXV infection.

Sex discrepancy in establishing mouse visceral obesity model induced by high-fat diet. / é«˜è„‚é¥®é£Ÿè¯±å¯¼çš„å† è„è‚¥èƒ–å°é¼ æ¨¡åž‹å­˜åœ¨æ€§åˆ«å·®å¼‚.

OBJECTIVES: To establish a mouse visceral obesity model, and to investigate the effect of animal sex on this model. METHODS: Thirty-two 4-week-old BALB/c mice were randomly divided into female control group, female high-fat group, male control group and male high-fat group with 8 mice in each group.The control groups were given ordinary diet, and the high-fat groups were given high-fat diet. After 12 weeks of feeding, body weight, visceral fat, fasting blood glucose, glucose tolerance, blood lipid and metabolism-related hormone levels were measured, and the composition of gut microbiota of mice was analyzed by 16S rRNA sequencing. RESULTS: The high fat diet resulted in a significant increase of body weight and visceral fat content in male mice; the pathological results showed significantly increased fat area, accumulation of liver fat droplets, increased total cholesterol, fasting blood glucose, oral glucose tolerance and serum insulin levels (all P<0.05), as well as significant insulin resistance (P<0.01). However, the above changes were not significant in female mice. Compared with the control groups, there was an increase in the relative abundance of obesity-related gut microbiota in the model groups (such as Blautia), and the microbiota structure changed significantly, while the changes were less obvious in female mice. CONCLUSIONS: A visceral obesity mouse model has been stably established by feeding high-fat diet in BALB/c male mice, showing visceral fat accumulation, metabolic dysfunction and gut microbiota changes; while female mice are not sensitive in this obesity model.

Serum Insulin-Like Growth Factor-Binding Protein 7 Deriving from Spleen and Lung Could Be Used for Early Recognition of Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. METHODS: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery and at inclusion (0 h), 2 h, 6 h, and 12 h after intensive care unit (ICU) admission, and compared with serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and serum uric acid (UA). RESULTS: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (sIGFBP7-2 h) was significantly higher in patients who developed AKI. The relationships between sIGFBP7-2 h in AKI patients and log2 (SCr), log2 (BUN), log2 (eGFR), and log2 (UA) were statistically significant. The diagnostic performance of sIGFBP7-2 h measured by the macro-averaged area under the receiver operating characteristic curve was 0.948 (95% CI, 0.853-1.000; p < 0.001). CONCLUSION: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.

circFANCA accelerates the malignant process of OSCC by modulating miR-34a/PA28γ signaling.

OBJECTIVES: To investigate the upstream regulatory molecules of proteasomal activator 28γ (PA28γ), and explore its specific regulatory mechanism and potential clinical significance in OSCC. MATERIALS AND METHODS: qPCR was used to examine miR-34a, circFANCA and PSME3 expression. Western blotting was adopted to detect PA28γ expression. Transwell experiments were conducted to evaluate OSCC cell migration and invasion ability. FISH was used to evaluate the subcellular localization of circFANCA and miR-34a, and RNA pull-down verified the interaction between them. The expression of circFANCA and miR-34a in clinical cohorts was assessed by ISH, and the results were subjected to survival analysis using Kaplan-Meier analysis. RESULTS: Here, we proved that miR-34a expression is lower in highly aggressive OSCC tissues and cell lines. Notably, miR-34a can downregulate PA28γ expression and inhibit OSCC invasion and migration. Next, we confirmed that circFANCA promoted OSCC cell metastatic ability by sponging miR-34a. Importantly, interfering with miR-34a rescued the malignant progression of OSCC induced by silencing circFANCA. Finally, clinical data showed lower miR-34a expression and higher circFANCA expression were associated with poor prognosis in OSCC patients. CONCLUSION: The circFANCA/miR-34a/PA28γ axis facilitates the metastasis of OSCC, and circFANCA and miR-34a have potential to serve as prognostic markers for OSCC patients.

Influence of Different pH Values on Gels Produced from Tea Polyphenols and Low Acyl Gellan Gum.

To explore the influence of pH values on the properties of a compound system containing tea polyphenols (TPs) and low acyl gellan gum (LGG), the color, texture characteristics, rheological properties, water holding capacity (WHC), and microstructure of the compound system were measured. The results showed that the pH value noticeably affects the color and WHC of compound gels. Gels from pH 3 to 5 were yellow, gels from pH 6 to 7 were light brown, and gels from pH 8 to 9 were dark brown. The hardness decreased and the springiness increased with an increase in pH. The steady shear results showed that the viscosity of the compound gel solutions with different pH values decreased with increasing shear rates, indicating that all of the compound gel solutions were pseudoplastic fluids. The dynamic frequency results showed that the G' and G″ of the compound gel solutions gradually decreased with increasing pH and that G' was higher than G″. No phase transition occurred in the gel state under heating or cooling conditions at pH 3, indicating that the pH 3 compound gel solution was elastic. The WHC of the pH 3 compound gel was only 79.97% but the WHC of compound gels pH 6 and pH 7 was almost 100%. The network structure of the gels was dense and stable under acidic conditions. The electrostatic repulsion between the carboxyl groups was shielded by H+ with increasing acidity. The three-dimensional network structure was easily formed by an increase in the interactions of the hydrogen bonds.