Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy.

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.

Myelin oligodendrocyte glycoprotein antibody-associated disease with clinical presentation as multiple episodes of isolated meningeal involvement: a case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.

Puerarin alleviates diabetic nephropathy by inhibiting Caspase-1-mediated pyroptosis.

BACKGROUND AND PURPOSE: Diabetic nephropathy (DN) is an important cause of end-stage renal disease, with podocyte injury as the main feature. Pyroptosis plays a non-negligible role in the process of diabetic nephropathy. Puerarin (PR) treatment of diabetic nephropathy has great potential, but the mechanism is not very clear. This article aims to study the protective effect and mechanism of puerarin on DN. METHODS: Streptozotocin (STZ)-induced C57 BL/6J mouse model of DN was given PR, Necrosulfomide (NSA), Nigericin for 12 weeks; A 60 mM high glucose(HG) induced MPC5 cell injury model was administered to PR, NSA, and Nigericin interventions for 24 h. RESULTS: After 12 weeks of administration, PR reduced fasting blood glucose levels in DN mice, alleviated glomerular lesions, reduced podocyte damage, and protected renal function. Meanwhile, PR also inhibits the expression of pyroptosis-related proteins. In addition, PR alleviated the release of Interleukin 18 (IL-18), Interleukin 1beta (IL-1ß), and lactate dehydrogenase (LDH) in MPC5 cells under HG conditions, downregulated the expression of pyrozozois-related proteins, and improved Caspase-1-mediated pyroptosis in MPC5 cells. CONCLUSION: Our study suggests that the beneficial effects of PR in diabetic nephropathy may be associated with inhibition of Caspase-1-mediated pyroptosis.

Efr3b is essential for social recognition by modulating the excitability of CA2 pyramidal neurons.

CA2 pyramidal neurons (PNs) are associated with social behaviors. The mechanisms, however, remain to be fully investigated. Here, we report that Efr3b, a protein essential for phospholipid metabolism at the plasma membrane, is widely expressed in the brain, especially in the hippocampal CA2/CA3 areas. To assess the functional significance of Efr3b in the brain, we generated Efr3bf/f mice and crossed them with Nestin-cre mice to delete Efr3b specifically in the brain. We find that Efr3b deficiency in the brain leads to deficits of social novelty recognition and hypoexcitability of CA2 PNs. We then knocked down the expression of Efr3b specifically in CA2 PNs of C57BL/6J mice, and our results showed that reducing Efr3b in CA2 PNs also resulted in deficits of social novelty recognition and hypoexcitability of CA2 PNs. More interestingly, restoring the expression of Efr3b in CA2 PNs enhances their excitability and improves social novelty recognition in Efr3b-deficient mice. Furthermore, direct activation of CA2 PNs with chemogenetics improves social behaviors in Efr3b-deficient mice. Together, our data suggest that Efr3b is essential for social novelty by modulating the excitability of CA2 PNs.

An eye tracking investigation of attention mechanism in driving behavior under emotional issues and cognitive load.

Emotions have specific effects on behavior. At present, studies are increasingly interested in how emotions affect driving behavior. We designed the experiment by combing driving tasks and eye tracking. DSM-V assessment scale was applied to evaluate the depression and manic for participants. In order to explore the dual impacts of emotional issues and cognitive load on attention mechanism, we defined the safety-related region as the area of interest (AOI) and quantified the concentration of eye tracking data. Participants with depression issues had lower AOI sample percentage and shorter AOI fixation duration under no external cognitive load. During our experiment, the depression group had the lowest accuracy in arithmetic quiz. Additionally, we used full connected network to detect the depression group from the control group, reached 83.33%. Our experiment supported that depression have negative influences on driving behavior. Participants with depression issues reduced attention to the safety-related region under no external cognitive load, they were more prone to have difficulties in multitasking when faced with high cognitive load. Besides, participants tended to reallocate more attention resources to the central area under high cognitive load, a phenomenon we called "visual centralization" in driving behavior.

Application of Cyclodextrin for Cancer Immunotherapy.

Tumor immunotherapy, compared with other treatment strategies, has the notable advantage of a long-term therapeutic effect for preventing metastasis and the recurrence of tumors, thus holding great potential for the future of advanced tumor therapy. However, due to the poor water solubility of immune modulators and immune escape properties of tumor cells, the treatment efficiency of immunotherapy is usually significantly reduced. Cyclodextrin (CD) has been repeatedly highlighted to be probably one of the most investigated building units for cancer therapy due to its elegant integration of an internal hydrophobic hollow cavity and an external hydrophilic outer surface. The application of CD for immunotherapy provides new opportunities for overcoming the aforementioned obstacles. However, there are few published reviews, to our knowledge, summarizing the use of CD for cancer immunotherapy. For this purpose, this paper provides a comprehensive summary on the application of CD for immunotherapy with an emphasis on the role, function, and reported strategies of CD in mediating immunotherapy. This review summarizes the research progress made in using CD for tumor immunotherapy, which will facilitate the generation of various CD-based immunotherapeutic delivery systems with superior anticancer efficacy.

PPARα is involved in high-fat diet-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Risk avoidance behaviors are essential for survival. "Uncontrollable" risk-taking behaviors in animals or humans may have severe adverse consequences. In humans, a large proportion of psychiatric disorders are accompanied by impairments in risk avoidance. Obesity is associated with psychiatric disorders. Peroxisome proliferator-activated receptor α (PPARα) takes part in regulating lipid metabolism and neuronal function. Here, we investigated the effect of high-fat diet (HFD)-induced obesity on risk avoidance and the role of PPARα in this behavior. Male PPARα-null (KO) mice and wild-type (WT) mice were assigned to four different groups: WT-CON and KO-CON (normal diet); WT-HFD and KO-HFD (high fat diet). The HFD began at week 6 and was continued until sampling. A series of behavioral tests were performed at week 11. We found that WT but not KO mice fed with a HFD exhibited weight gain and risk avoidance impairment, compared with the mice fed with a normal diet. The staining of c-Fos revealed that the hippocampus was the main brain region involved in risk avoidance behavior. Moreover, biochemical analysis suggested that the decreased levels of the brain-derived neurotrophic factor (BDNF) in the hippocampus might contribute to risk avoidance impairment induced by a HFD. These results indicated that PPARα is involved in HFD-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Experimental Study on Bubble Dynamics and Mass Transfer Characteristics of Coaxial Bubbles in Petroleum-Based Liquids.

Petroleum-based liquids are from an important petroleum-based polymer, whose application and preparation involve multiple operations related to gas-liquid two-phase flow. Due to insufficient research on gas-liquid two-phase flow, there is a gap in bubble dynamics and mass transfer characteristics in petroleum-based liquids. Accordingly, we have systematically investigated the bubble formation process, bubble rising dynamics, and mass transfer of coaxial bubbles. Herein, the contour of bubbles was obtained for analyzing the bubble formation process. It was found that the increase of gas flow rate contributed to the increase of bubble generation size, while the liquid viscosity had an inhibitory influence on the increase of bubble generation size. Moreover, the variation of bubble rising velocity was considered and the force analysis of the rising bubble was provided. A new model of drag coefficient applicable to petroleum-based liquids was proposed. Finally, variations in the amount of dissolved oxygen in the liquid were measured to analyze the mass transfer characteristics. The increase in nozzle inner diameter and gas flow rate both promoted mass transfer, but the increased liquid viscosity hindered mass transfer.

Erratum to "Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model".

[This corrects the article on p. 336 in vol. 7, PMID: 27493838.].

Aberrant serotonergic signaling contributes to the hyperexcitability of CA1 pyramidal neurons in a mouse model of Alzheimer's disease.

Hyperactivity of pyramidal neurons (PNs) in CA1 is an early event in Alzheimer's disease. However, factors accounting for the hyperactivity of CA1 PNs remain to be completely investigated. In the present study, we report that the serotonergic signaling is abnormal in the hippocampus of hAPP-J20 mice. Interestingly, chemogenetic activation of serotonin (5-hydroxytryptamine; 5-HT) neurons in the median raphe nucleus (MRN) attenuates the activity of CA1 PNs in hAPP-J20 mice by regulating the intrinsic properties or inhibitory synaptic transmission of CA1 PNs through 5-HT3aR and/or 5-HT1aR. Furthermore, activating MRN 5-HT neurons improves memory in hAPP-J20 mice, and this effect is mediated by 5-HT3aR and 5-HT1aR. Direct activation of 5-HT3aR and 5-HT1aR with their selective agonists also improves the memory of hAPP-J20 mice. Together, we identify the impaired 5-HT/5-HT3aR and/or 5-HT/5-HT1aR signaling as pathways contributing to the hyperexcitability of CA1 PNs and the impaired cognition in hAPP-J20 mice.

Barrier-penetrating liposome targeted delivery of basic fibroblast growth factor for spinal cord injury repair.

Nanoparticle technologies offer a non-invasive means to deliver basic fibroblast growth factor (bFGF) for the treatment of spinal cord injury (SCI). However, the inability of bFGF to accumulate at the injury site and inefficient penetration across the blood-spinal cord barrier (BSCB) remain challenges. The present study describes a dual-targeting liposome (bFGF@Lip-Cp&Rp) with injury lesion targeting and BSCB-penetrating capability to deliver bFGF for SCI treatment. The CAQK peptide (Cp) with injury lesion targeting ability and R2KC peptide (Rp) with BSCB-penetrating capability were grafted onto the liposomes for a flexible and non-invasive drug delivery systems preparation. Results exhibit that the dual-targeted liposomes could significantly cross the BSCB and accumulate at the injury site. During the early stage of SCI, bFGF@Lip-Cp&Rp promotes repair of BSCB and facilitates M2-polarization of macrophages. Regular delivery of bFGF@Lip-Cp&Rp increase HUVECs tube formation and angiogenesis, ameliorate the microenvironment of lesion site, suppress the neuronal apoptosis and axonal atrophy in SCI rats. Importantly, continuous treatment of bFGF@Lip-Cp&Rp supports the restoration of limb motor function in SCI rats. In summary, this research implies that the injury site-targeting and BSCB-penetrating liposomes could be a promising therapeutic approach for the treatment of SCI.

Highly Specific Antibiotic Detection on Water-Stable Black Phosphorus Field-Effect Transistors.

Two-dimensional (2D) black phosphorus (BP) has been reported to have appealing semiconducting properties as the sensing channel in field-effect transistor (FET) sensors. However, the intrinsic instability of BP in water greatly hinders its application, and little is known about its sensing performance and mechanism in aqueous medium. Herein, a water-stable BP FET sensor for antibiotic detection is reported. A novel surface engineering strategy with Ag+ coordination and melamine cyanurate (MC) supramolecular passivation is utilized to enhance the stability and transistor performance of BP. With molecularly imprinted polymers (MIPs) as the detection probe for tetracycline, the BPAg(+)/MC/MIPs sensor shows high sensitivity to tetracycline with a detection limit of 7.94 nM and a quick response within 6 s as well as high selectivity against other antibiotics with similar molecular structures. A new sensing mechanism relying on the conjugation effect of the probe structure is proposed, and new knowledge about alkalinity-enhanced and ionic strength-related response from the electrostatic gating effect is given based on the solution chemistry impact study. This work offers an efficient surface engineering strategy to enable the application of 2D BP for antibiotic detection in aqueous medium and presents a new sensing mechanism in chemical analysis by FET sensors.

Fast, specific, and ultrasensitive antibiotic residue detection by monolayer WS2-based field-effect transistor sensor.

Antibiotic residues cause increasing concern in environmental ecology and public health, which needs efficient analysis strategy for monitoring and control. In this study, a fast, specific, and ultrasensitive sensor based on field-effect transistor (FET) has been proposed for the detection of ampicillin (AMP). The sensor involves monolayer tungsten disulfide (WS2) nanosheet as the sensing channel, single-stranded DNA (ssDNA) as the sensing probe, and gold nanoparticle (Au NP) as the linker. The WS2/Au/ssDNA FET sensor responds rapidly to AMP in a wide linear detection range (10-12-10-6 M) and has low limit of detection (0.556 pM), which meets the permissible standards of AMP in water and food. The sensing mechanism study suggests that the excellent sensor response results from the increased number of negative charges in the Debye length and the consequent accumulation of holes in WS2 channel after the addition of AMP. Moreover, satisfactory sensing performance was confirmed in real water samples, indicating the potential application of the proposed method in practical AMP detection. The reported FET sensing strategy provides new insights in antibiotic analysis for risk assessment and control.

Impaired orienting function detected through eye movements in patients with temporal lobe epilepsy.

Objective: Patients with temporal lobe epilepsy (TLE) often exhibit attention function impairment. The orienting network is the subsystem of the attention network that has not been fully studied. In this study, we used eye-tracking technology with an attention network test (ANT)-based task to assess the orienting function of TLE patients, aiming to characterize their eye movement patterns. Methods: A total of 37 TLE patients and 29 healthy controls (HCs) completed the ANT task based on eye-tracking technology. Orienting function damage was mainly assessed by the ANT orienting effect. Eye movement metrics, such as mean first goal-directed saccade latency (MGSL), total saccades, and saccade amplitudes, were compared between groups. Results: The TLE patients had a significantly lower ANT orienting effect (HC, 54.05 ± 34.05; TLE, 32.29 ± 39.54) and lower eye-tracking orienting effect (HC, 116.98 ± 56.59; TLE, 86.72 ± 59.10) than those of the HCs. The larger orienting effects indicate that orienting responses are faster when receiving a spatial cue compared with a center cue. In the spatial cue condition, compared with HCs, the TLE group showed a longer first goal-directed saccade latency (HC, 76.77 ± 58.87 ms; TLE, 115.14 ± 59.15 ms), more total saccades (HC, 28.46 ± 12.30; TLE, 36.69 ± 15.13), and larger saccade amplitudes (HC, 0.75° ± 0.60°; TLE, 1.36° ± 0.89°). Furthermore, there was a positive correlation of the orienting-effect score between the ANT task and eye-tracking metrics (r = 0.58, p < 0.05). Conclusion: We innovatively developed a new detection method using eye-tracking technology in combination with an ANT-based task to detect the orienting function in TLE patients. The current research demonstrated that TLE patients had a significant orienting dysfunction with a specific saccade pattern characterized by a longer first goal-directed saccade latency, more total saccades, and larger saccade amplitudes. These oculomotor metrics are likely to be a better indicator of orienting function and may potentially be used for behavioral-based interventions and long-term cognition monitoring in TLE patients.

The neuropeptide Y single-nucleotide polymorphism rs16147:T>C moderates the effect of alcohol dependence on depression in male Chinese Han population.

Background: Previous studies suggest that alcohol dependence is associated with depression, however, the effect of alcohol dependence varies from individual to individual, which may be due to different genetic backgrounds. The interactions between alcohol dependence and different gene polymorphisms may finally shape the onset of depression. Neuropeptide Y (NPY), which can maintain homeostasis from high-stress stimulation, may protect individuals from the onset of depression. Here, we explored whether the NPY rs16147:T>C has an association with depression in individuals with alcohol dependence during the period of alcohol dependence withdrawal. Methods: A total of 455 males with alcohol dependence were recruited. The scale of Michigan Alcoholism Screening Test (MAST) and Self-Depression Scale (SDS) were respectively used to analyze the condition of alcohol dependence and depression. Genomic DNA was extracted from each blood sample and NPY polymorphisms were genotyped. The interaction between NPY rs16147:T>C and alcohol dependence on depression was first analyzed. Then, region of significance analysis was used to confirm which model provided the best fit for the interaction (diathesis-stress or differential susceptibility). Finally, by using internal replication analyses, the accuracy and robustness of the interaction results were improved. Results: Alcohol dependence was positively correlated with depression. CC homozygotes of NPY rs16147:T>C exhibited less depression when exposed to low alcohol dependence, but more depression when exposed to high alcohol dependence. Individuals with the T allele showed the opposite result. Conclusion: NPY rs16147:T>C might be correlated with susceptibility for depression in males during alcohol dependence withdrawal. The findings support the differential susceptibility model.

An Eye Tracking and Event-Related Potentials Study With Visual Stimuli for Adolescents Emotional Issues.

Background: Psychological issues are common among adolescents, which have a significant impact on their growth and development. However, the underlying neural mechanisms of viewing visual stimuli in adolescents are poorly understood. Materials and Methods: This study applied the Chinese version of the DSM-V self-assessment scales to evaluate 73 adolescents' psychological characteristics for depressive and manic emotional issues. Combined with eye-tracking and event-related potential (ERP), we explored the characteristics of their visual attention and neural processing mechanisms while freely viewing positive, dysphoric, threatening and neutral visual stimuli. Results: Compared to controls, adolescents with depressive emotional tendencies showed more concentrated looking behavior with fixation distribution index than the controls, while adolescents with manic emotional tendencies showed no such trait. ERP data revealed individuals with depressive tendencies showed lower arousal levels toward emotional stimuli in the early stage of cognitive processing (N1 amplitude decreased) and with prolonged reaction time (N1 latency increased) than the control group. We found no significant difference between the manic group and the control group. Furthermore, the depression severity scores of the individuals with depressive tendencies were negatively correlated with the total fixation time toward positive stimuli, were negatively correlated with the fixation distribution index toward threatening stimuli, and were positively correlated with the mean N1 amplitudes while viewing dysphoric stimuli. Also, for the individuals with depressive tendencies, there was a positive correlation between the mean N1 amplitudes and the fixation time on the area of interest (AOI) while viewing dysphoric stimuli. For the individuals with manic tendencies, the manic severity scores of the individuals with manic tendencies were positively correlated with the total fixation time toward the positive stimuli. However, no significant correlations were found between the manic severity scores and N1 amplitudes, and between N1 amplitudes and eye-tracking output variables. Conclusion: This study proposes the application of eye-tracking and ERP to provide better biological evidence to alter the neural processing of emotional stimuli for adolescents with emotional issues.

Measurement and Prediction of Isothermal Vapor-Liquid Equilibrium and Thermodynamic Properties of a Turpentine + Rosin System Using the COSMO-RS Model.

The vapor-liquid equilibrium (VLE) of components of a turpentine + rosin system were measured at 313.2 and 333.2 K using headspace gas chromatography. The thermodynamic properties of the turpentine + rosin system such as activity coefficients, total pressure, partial pressure, excess Gibbs energies, and excess enthalpies were calculated using the COSMO-RS model. The results showed that the activity coefficients were greater than 1 for all components of turpentine except for longifolene, indicating a positive deviation from Raoult's law for all components of turpentine except for longifolene. The total pressures were about 1 kPa at 313.2 K and about 3 kPa at 333.2 K. Meanwhile, the excess Gibbs energies G E and excess enthalpies H E of the system were positive, indicating that the mixing of the components of turpentine and rosin was endothermic. Moreover, the hydrogen bonding interaction energy H E(hydrogen bonding) contributed the most for the excess enthalpies H E.

Promotion of Phenol Electro-oxidation by Oxygen Evolution Reaction on an Active Electrode for Efficient Pollution Control and Hydrogen Evolution.

We report an electrolysis system using NiFe layered double hydroxide/CoMoO4/nickel foam (NFLDH/CMO/NF) as the anode and CMO/NF as the cathode for simultaneous phenol electro-oxidation and water electrolysis. This system shows high performance for both phenol degradation and hydrogen evolution. We demonstrate that the degradation rate of phenol on the active anode is governed by the mass transfer rate at a low phenol concentration (0.5-2 mM) and by the electro-oxidation rate at a high phenol concentration (5 mM). The anodic oxygen evolution reaction (OER) can promote the phenol degradation through enhanced mass transfer efficiency. More importantly, the common deactivation issue of phenol electro-oxidation on the inert anode can be eliminated by the high OER activity of the active anode. The constructed full electrolytic cell only needs a low potential of 1.498 V to achieve 10 mA/cm2 for water electrolysis. The reported promotion effect of phenol degradation by OER as well as the improved anode resistance to deactivation offer new insights into efficient and robust waste-to-resource electrolysis system for water treatment.

Experimental Determination and Computational Prediction of Dehydroabietic Acid Solubility in (-)-α-Pinene + (-)-ß-Caryophyllene + P-Cymene System.

The solubility of dehydroabietic acid in (-)-α-pinene, p-cymene, (-)-ß-caryophyllene, (-)-α-pinene + p-cymene, (-)-ß-caryophyllene + p-cymene and (-)-α-pinene + (-)-ß-caryophyllene were determined using the laser monitoring method at atmospheric pressure. The solubility of dehydroabietic acid was positively correlated with temperature from 295.15 to 339.46 K. (-)-α-pinene, p-cymene, and (-)-ß-caryophyllene were found to be suitable for the solubilization of dehydroabietic acid. In addition, the non-random two liquid (NRTL), universal quasi-chemical (UNIQUAC), modified Apelblat, modified Wilson, modified Wilson-van't Hoff, and λh models were applied to correlate the determined solubility data. The modified Apelblat model gave the minor deviation for dehydroabietic acid in monosolvents, while the λh equation showed the best result in the binary solvents. A comparative analysis of compatibility between solutes and solvents was carried out using Hansen solubility parameters. The thermodynamic functions of ΔsolH0, ΔsolS0, ΔsolG0 were calculated according to the van't Hoff equation, indicating that the dissolution was an entropy-driven heat absorption process. The Conductor-like Screening Model for Real Solvents (COSMO-RS) combined with an experimental value was applied to predict the reasonable solubility data of dehydroabietic acid in the selected solvents systems. The interaction energy of the dehydroabietic acid with the solvent was analyzed by COSMO-RS.