Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Nomogram prediction model for the risk of intracranial hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.

Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT. Methods: Retrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA). Results: A total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161-1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004-1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082-6.262; p < 0.001), systolic blood pressure (SBP) (OR, 1.039; 95% CI, 1.009-1.075; p = 0.016) were the independent predictors of HT which were used to generate nomogram. The nomogram showed good discrimination due to AUC-ROC values. Calibration plot showed good calibration. DCA showed that nomogram is clinically useful. Conclusion: Nomogram consisting of NIHSS, NT-pro BNP, NLR, SBP scores predict the risk of HT in AIS patients treated with IVT.

Can We Do Breast-Conserving Surgery Without Intraoperative Frozen Section of Margin?

PURPOSE: This study was a retrospective and nonrandomized study to assess the safety and reliability of identifying the surgical margin in breast cancer breast-conserving surgery (BCS) by using intraoperative ultrasonic location and specimen mammography instead of traditional intraoperative frozen pathological section. METHODS: Among the patients who underwent BCS from May 2019 to October 2021, according to the different methods of evaluating the intraoperative margin, 104 breast cancer patients were included in the frozen edge group, 53 breast cancer patients were included in the freeze-free group, and the surgeon judged whether extended resection was needed based on the results of pathological section or evaluation of intraoperative ultrasound and mammography. The surgical margins of the two groups were judged by postoperative pathological results as the gold standard. RESULTS: The median waiting pathology results time in the frozen edge group was 64 minutes, while the waiting time in the freeze-free group was 30 minutes, and the difference was statistically significant (P < .0001). The postoperative pathological results showed that the positive rate of the surgical margin in the frozen edge group was 0.96%. The coincidence rate of intraoperative frozen and postoperative pathological results was 99.04%. The coincidence rate between intraoperative mammography and postoperative pathological results was 100%. CONCLUSIONS: In BCS, the method of using intraoperative staining markers combined with mammography to evaluate the resection margin is highly accurate, reliable, economical and convenient, and at the same time reduces the waiting time of the operator during the operation. However, this was not a randomized controlled study, and there was patient selection bias, and its safety needs to be confirmed by long-term follow-up. In the future, it is expected to become the mainstream means of evaluating.

Repetitive peripheral magnetic stimulation combined with transcranial magnetic stimulation in rehabilitation of upper extremity hemiparesis following stroke: a pilot study.

OBJECTIVE: To investigate the effect of combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation on upper extremity function in subacute stroke patients. DESIGN: Pilot study. SUBJECTS: Subacute stroke patients. METHODS: Included patients were randomized into 3 groups: a central-associated peripheral stimulation (CPS) group, a central-stimulation-only (CS) group, and a control (C) group. The CPS group underwent a new paired associative stimulation (combined repetitive peripheral magnetic stimulation and transcranial magnetic stimulation), the CS group underwent repetitive transcranial magnetic stimulation, and the C group underwent sham stimulation. All 3 groups received physiotherapy after the stimulation or sham stimulation. The treatment comprised 20 once-daily sessions. Primary outcome was the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score, and secondary outcomes were the Barthel Index and Comprehensive Functional Assessment scores, and neurophysiological assessments were mainly short-interval intracortical inhibition. A 3-group (CPS, CS, C) × 2-time (before, after intervention) repeated measures analysis of variance was conducted to determine whether changes in scores were significantly different between the 3 groups. RESULTS: A total of 45 patients were included in the analysis. Between-group comparisons on the FMA-UE demonstrated a significant improvement (group × time interaction, F2,42 = 4.86; p = 0.013; C vs CS, p = 0.020; C vs CPS, p = 0.016; CS vs CPS, p = 0.955). Correlation analysis did not find any substantial positive correlation between changes in FMA-UE and short-interval intracortical inhibition variables (C, r = -0.196, p = 0.483; CS, r = -0.169, p = 0.546; CPS, r = -0.424, p = 0.115). CONCLUSION: This study suggests that the real-stimulus (CS and CPS) groups had better outcomes than the control (C) group. In addition, the CPS group showed a better trend in clinical and neurophysiological assessments compared with the CS group.

Why does HER2-positive breast cancer metastasize to the brain and what can we do about it?

Breast cancer is the most frequent malignancy in women. However, in the middle and late stages, some people develop distant metastases, which considerably lower the quality of life and life expectancy. The brain is one of the sites where metastasis frequently happens. According to epidemiological research, brain metastases occur at a late stage in 30-50% of patients with HER2-positive breast cancer, resulting in a poor prognosis. Additionally, few treatments are available for HER2-positive brain metastatic breast cancer, and the mortality rate is remarkable owing to the complexity of the brain's anatomical structure and physiological function. In this review, we described the stages of the brain metastasis of breast cancer, the relationship between the microenvironment and metastatic cancer cells, and the unique molecular and cellular mechanisms. It involves cancer cells migrating, invading, and adhering to the brain; penetrating the blood-brain barrier; interacting with brain cells; and activating signal pathways once inside the brain. Finally, we reviewed current clinically used treatment approaches for brain metastasis in HER2-positive breast cancer; summarized the traditional treatment, targeted treatment, immunotherapy, and other treatment modalities; compared the benefits and drawbacks of each approach; discussed treatment challenges; and emphasized the importance of identifying potential targets to improve patient survival rates and comprehend brain metastasis in breast cancer.

Impacts of adjustment of National Reimbursement Drug List on orphan drugs volume and spending in China: an interrupted time series analysis.

OBJECTIVE: To evaluate the impacts of the 2017 adjustment of National Reimbursement Drug List (NRDL) on orphan drugs hospital procurement volumes and spending in China. DESIGN: We used an interrupted time series design covering the period from 2016 to 2018 to analyse changes in hospital procurement volumes and spending of orphan drugs for which were included in the 2017 NRDL. SETTING AND DATA: The study was conducted in China. Orphan drug procurement data of 789 public hospitals (594 tertiary hospitals and 195 secondary hospitals) were derived from the Chinese Medical Economic Information (CMEI). OUTCOME MEASURES: Monthly orphan drugs hospital procurement volumes and spending. RESULTS: Nine orphan drugs were included in the 2017 NRDL (seven were directly included, and two were included after price negotiation). Comparing to orphan drugs not included in the NRDL, hospital procurement volumes ([Formula: see text] =43 312, p<0.001) and spending ([Formula: see text] =6 48 927, p<0.001) of the nine included drugs showed significant upward trends after implementation of the 2017 NRDL adjustment. CONCLUSIONS: Our results suggest that the 2017 adjustment of NRDL significantly changed the usage and spending on certain orphan drugs. The increase in orphan drug hospital procurement volumes should improve rare disease patients' access to these orphan drugs.

Multi-functional device: manipulating linear and circular-polarization conversion in a terahertz chiral metamaterial.

We propose a terahertz chiral metamaterial as a multi-functional device to manipulate asymmetry transmission of linear polarized waves, linear-to-elliptical polarization conversion and circular dichroism in transmission mode while asymmetry reflection of circular polarized waves. For incidence of linear polarized waves, dual-band asymmetry transmission is shown around 0.42 THz and 1.04 THz where asymmetry transmission factors reach up to two peak values: ∼0.51 and ∼0.55, respectively. Intense linear-to-elliptical polarization conversion occurs at 0.81 THz and 0.97 THz, respectively. For incidence of circular polarized waves, a strong circular dichroism appears at 0.36 THz where circular dichroism parameter reaches to ∼0.64 and asymmetry reflection is displayed around 0.36 THz with the maximum of asymmetry reflection factors approaching to 0.55.

Ultrasensitive Flexible Thermal Sensor Arrays based on High-Thermopower Ionic Thermoelectric Hydrogel.

Ionic circuits using ions as charge carriers have demonstrated great potential for flexible and bioinspired electronics. The emerging ionic thermoelectric (iTE) materials can generate a potential difference by virtue of selective thermal diffusion of ions, which provide a new route for thermal sensing with the merits of high flexibility, low cost, and high thermopower. Here, ultrasensitive flexible thermal sensor arrays based on an iTE hydrogel consisting of polyquaternium-10 (PQ-10), a cellulose derivative, as the polymer matrix and sodium hydroxide (NaOH) as the ion source are reported. The developed PQ-10/NaOH iTE hydrogel achieves a thermopower of 24.17 mV K-1 , which is among the highest values reported for biopolymer-based iTE materials. The high p-type thermopower can be attributed to thermodiffusion of Na+ ions under a temperature gradient, while the movement of OH- ions is impeded by the strong electrostatic interaction with the positively charged quaternary amine groups of PQ-10. Flexible thermal sensor arrays are developed through patterning the PQ-10/NaOH iTE hydrogel on flexible printed circuit boards, which can perceive spatial thermal signals with high sensitivity. A smart glove integrated with multiple thermal sensor arrays is further demonstrated, which endows a prosthetic hand with thermal sensation for human-machine interaction.

Flexible Te/PEDOT:PSS thin films with high thermoelectric power factor and their application as flexible temperature sensors.

Flexible, lightweight, and low-cost thermoelectric thin films are promising for self-powered wearable electronics and sensors. In this work, we report on flexible Te nanostructures/PEDOT:PSS composite thin films with high power factor and their application as flexible temperature sensors. Te nanostructures with high crystallinity and high aspect ratios were synthesized through an environmentally friendly method without using highly toxic chemicals. Individual Te nanostructures achieve a thermoelectric figure of merit (ZT) of 0.13 at 300 K, indicating good potential as inorganic fillers for nanostructures/polymer hybrid materials. Based on the synthesized Te nanostructures, flexible p-type Te/PEDOT:PSS thin films were fabricated through a simple dilution and vacuum filtration method. The power factor of the as-prepared composite thin film outperforms that of either a Te or DMSO-treated PEDOT:PSS thin film, and importantly, it can be further enhanced to 149 µW m-1 K-2 by hot pressing, which is nearly threefold enhancement compared to the values reported for the vacuum-filtered flexible Te/PEDOT:PSS thin films in the literature. The hot-pressed composite thin film shows high flexibility with the electrical conductivity remaining almost unchanged after 1000 bending cycles under a bending radius of 5 mm. Flexible temperature sensors were fabricated based on the hot-pressed Te/PEDOT:PSS thin film, which exhibited high sensitivity in detecting temperature stimuli. The developed temperature sensors were applied onto a two-finger flexible mechanical claw for identifying hot/cold objects in robotic grasping. This work demonstrates an effective approach to enhance the thermoelectric power factor of flexible Te nanostructures/polymer composites and their promising application in flexible thermal sensing.

Vanadium-induced synthesis of amorphous V-Co-P nanoparticles for an enhanced hydrogen evolution reaction.

The hydrogen evolution reaction (HER) plays a vital role for the production of pure hydrogen with zero carbon release. Developing high efficiency non-noble metal electrocatalysts could reduce its cost. Here, vanadium doped cobalt phosphide grown on carbon cloth (CC) was synthesized by the low temperature electrodeposition-phosphorization method. The influence of V dopants on the structural, morphological, and electrocatalytic performance of Vx-Co1-x-P composites was also investigated in-depth. Impressively, the optimized amorphous V0.1-Co0.9-P nano-electrocatalyst exhibits outstanding catalytic activity with a low overpotential of 50 mV at a current density of 10 mA cm-2 and a small Tafel value of 48.5 mV dec-1 in alkaline media. The results showed that V dopants in the composite change its crystal structure from the crystalline phase to the amorphous phase, resulting in the introduction of V-O sites, which regulate the electron density of the active sites and the exposure of surface active sites and thus promote the electrocatalytic HER process. This work provides a novel idea for the fabrication of high-efficiency metal phosphide based electrocatalysts.

A prognostic signature associated with cell senescence predicts survival outcomes and strongly associates with immunotherapy and chemotherapy response in breast cancer.

The objective of this study is to assess the predictive potency of cell senescence-related genes (CSRGs) in breast cancer (BC) and establish a risk signature. Trascriptome data of CSRGs were obtained from the TCGA and GEO databases. Consensus clustering was used to generate CSRGs-based molecular clusters for BC patients. A CSRGs-derived risk signature was built using multiple Cox regression analyses of differentially expressed genes (DEGs) between clusters. The prognosis, immune infiltration, chemotherapy and immunotherapy response between different risk groups were analyzed and compared. Two molecular clusters of BC patients were generated on the basis of 79 differentially expressed CSRGs, which showed distinct prognosis and immune infiltration. A total of 1403 DEGs between the CSRGs-derived clusters were found, and 10 of them were independent prognostic genes that used to construct a risk signature. The results demonstrated that patients with older age and advanced stage presented with a higher risk scores. In addition, the risk signature was found to be associated with outcomes, immune infiltration, chemotherapy and immunotherapy response. Patients in the low-risk group showed a favorable prognosis and higher immunotherapy response than those in the high-risk group. Finally, we developed a highly stable nomogram that incorporates risk signature, chemotherapy, radiotherapy, and stage variables, enabling accurate prediction of the overall survival (OS) of individual patients. To conclude, the signature derived from CSRGs holds great promise as a biomarker for prognostic assessment of BC and may serve as a valuable tool in guiding immunotherapy.

Hierarchical CdS/Ni3S4/Ni2P@C Photocatalyst for Efficient H2 Evolution under Visible-Light Irradiation.

Structural and morphological modulations play a crucial role in increasing the surface active sites of semiconductor photocatalysts for visible-light-driven water splitting. To fabricate a novel CdS/Ni3S4/Ni2P@C heterostructure, we first prepared carbon-encapsulated Ni3S4/Ni2P (Ni3S4/Ni2P@C) with a high surface area by sequential carbonization and phosphorization of a Ni-metal-organic framework (MOF) precursor. Combined characterization and photoelectrochemical measurement results reveal that the assembly of CdS nanowires and highly porous Ni3S4/Ni2P@C can enhance the visible-light response capability of the CdS/Ni3S4/Ni2P@C heterostructure catalyst by reducing the forbidden band gap of CdS. The hydrogen production rate of 21.56 mmol h-1 g-1 for CdS/Ni3S4/Ni2P@C with a Ni3S4/Ni2P@C mass fraction of 10 wt % was 26 times higher than that of CdS in a photolytic aquatic hydrogen system. A possible mechanism for the photocatalytic enhancement of the Ni3S4/Ni2P@C co-catalyst was systematically investigated and discussed. This research opens a new strategy for constructing ternary heterojunction photocatalysts via MOF precursors.

Rolling Circle Amplification-Based DNA Nano-Assembly for Targeted Drug Delivery and Gene Therapy.

Combining the killing ability of chemotherapy drugs on tumor cells with the inhibiting ability of genetic drugs on tumor cell growth, a dual drug delivery system loaded with therapy drugs and siRNA has gradually received more and more research and extensive attention. In this paper, we designed a DNA nano-assembly based on rolling circle amplification that can co-deliver doxorubicin (Dox) and siRNA simultaneously. In order to fully exploit the potential of the dual loading system in cancer treatment, we selected STAT3 gene as a target and used siRNA to target STAT3 of mRNA and reduce the STAT3 expression in mouse melanoma cell line (B16); meanwhile, Dox as a chemotherapy drug was combined with multivalent aptamers specifically targeting B16 to achieve efficient delivery of siRNA and Dox. The results showed that the synergistic delivery system could achieve high efficiency in targeting and inhibiting proliferation in mouse melanoma cells. In addition, the synergistic effect of the dual delivery system on apoptosis of cancer cells was significantly better than that of single drug delivery systems.

Synthetic aperture rainbow refractometry.

This work proposed a synthetic aperture rainbow refractometry (SARR) by synthesizing rainbow signals of the same droplet with dual-wavelength laser beams, in order to increase the aperture of rainbow refractometry. In this way, the SARR can apply to long distance and small droplets measurement. An achromatic imaging system, which simultaneously records while separating the two rainbow signals in two channels of a color image, is elaborately designed. A data processing algorithm is developed to retrieve the optimal droplet refractive index and size. Numerical simulations of different droplet sizes from 10 µm to 200 µm certify the viability of the SARR. Proof-of-concept experiments of micron-sized ethanol droplets are performed with 1650 mm measurement distance. Results show that the SARR can accurately measure droplet refractive index and size with uncertainties of 2.3 × 10-4 and 2µm, respectively. The feasibility and accuracy of the proposed SARR are successfully demonstrated, paving the way for rainbow refractometry applied to large-scale industrial applications.

Experimental Evidence of Superdiffusive Thermal Transport in Si0.4Ge0.6 Thin Films.

Superdiffusive thermal transport represents a unique phenomenon in heat conduction, which is characterized by a size (L) dependence of thermal conductivity (κ) in the form of κ ∝ Lß with a constant ß between 0 and 1. Although superdiffusive thermal transport has been theoretically predicted for SiGe alloys, direct experimental evidence is still lacking. Here, we report on a systematic experimental study of the thickness-dependent thermal conductivity of Si0.4Ge0.6 thin films grown by molecular beam epitaxy. The cross-plane thermal conductivity of Si0.4Ge0.6 thin films spanning a thickness range from 20 to 1120 nm was measured in the temperature range 120-320 K via a differential three-omega method. Results show that the thermal conductivity follows a consistent κ ∝ t0.26 power law with the film thickness (t) at different temperatures, providing direct experimental evidence that alloy-scattering dominated thermal transport in SiGe is superdiffusive.

Assessing bilateral ankle proprioceptive acuity in stroke survivors: An exploratory study.

Background: Bilateral proprioception deficits were reported in stroke survivors. However, whether bilateral proprioception deficits exist in the ankle joint after stroke was unclear. Ankle proprioception is a significant predictor of balance dysfunction after stroke, and previous studies to date are lacking appropriate evaluation methods. Objectives: We want to determine whether the active movement extent discrimination apparatus (AMEDA) is a reliable tool for assessing ankle proprioceptive acuity in stroke survivors and the presence of deficits in ankle proprioception on the affected and unaffected sides in patients after stroke. Methods: Bilateral ankle proprioception was assessed in 20 stroke patients and 20 age-matched healthy controls using AMEDA. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Results: The ICC in the affected and unaffected sides was 0.713 and 0.74, respectively. Analysis of variance revealed significant deficits in ankle proprioception in subacute stroke survivors vs. healthy controls (F = 2.719, p = 0.045). However, there were no significant differences in proprioception acuity scores between the affected and unaffected sides in patients after stroke (F = 1.14, p = 0.331). Conclusions: Stroke survivors had bilateral deficits in ankle proprioceptive acuity during active movements compared with age-matched healthy controls, underscoring the need to evaluate these deficits on both sides of the body and develop effective sensorimotor rehabilitation methods for this patient population. The AMEDA can reliably determine bilateral ankle proprioceptive acuity in stroke survivors.

Why Does Doxycycline Pose a Relatively Low Risk for Promotion of Clostridioides difficile Infection?

Background: Clinical studies suggest that doxycycline poses a low risk for promotion of Clostridioides difficile infection, but the microbiologic explanation for this finding is unclear. Methods: Mice treated with oral doxycycline, oral azithromycin, subcutaneous ceftriaxone, doxycycline plus ceftriaxone, or azithromycin plus ceftriaxone were challenged with 104 colony-forming units of 2 different C. difficile strains on day 2 of 5 of treatment. The concentration of C. difficile was measured in stool 2 and 5 days after challenge. The impact of the treatments on the microbiota was assessed by sequencing. Results: Doxycycline and azithromycin treatment did not promote colonization by either C. difficile strain in comparison to saline controls. Doxycycline treatment significantly reduced ceftriaxone-induced overgrowth of a C. difficile strain with doxycycline minimum-inhibitory concentration (MIC) of 0.06 µg/mL (P<0.01) but not a strain with doxycycline MIC of 48 µg/mL (P>0.05); azithromycin treatment did not reduce ceftriaxone-induced overgrowth of either strain. 16S rRNA amplicon sequencing revealed significantly lower bacterial diversity in the stool of ceftriaxone-treated mice, in comparison to doxycycline-treated and azithromycin-treated mice. Conclusions: These findings suggest that doxycycline may have a low propensity to promote C. difficile colonization because it causes relatively limited alteration of the indigenous microbiota that provide colonization resistance and because it provides inhibitory activity against some C. difficile strains.

Zebrafish xenograft model for studying the function of lncRNA SNHG4 in the proliferation and migration of colorectal cancer.

Background: The zebrafish xenograft model has become a reliable in vivo model for human cancer research. Compared to a mouse model, the zebrafish xenograft has many advantages, including optical transparency, intuitive in vivo observation, and speed. Long noncoding RNAs (lncRNAs) have been identified as crucial regulatory factors in the progression of colorectal cancer (CRC). The biological function of lncRNA small nucleolar RNA host gene 4 (SNHG4) in CRC is still unclear. Methods: We analyzed the expression of SNHG4 in CRC patient samples by the Gene Expression Profiling Interactive Analysis (GEPIA) software. The quantitative real time-polymerase chain reaction (qRT-PCR) was used to verify in CRC cell lines. The colony formation assay was used to study the cell proliferation, and we used the transwell assay to detect the migration ability. Then the zebrafish xenograft models were used to confirm these roles of SNHG4 in vivo. Moreover, we detected epithelial mesenchymal transition (EMT) related genes by qRT-PCR. Results: We found the expression of SNHG4 was upregulated in CRC patient samples by analyzing GEPIA software, which was also verified in CRC cell lines. We also found that silencing SNHG4 inhibited the proliferation and migration of CRC cells, and its roles were verified in zebrafish xenografts in vivo. Further, we found that the expression of E-cadherin was significantly upregulated and N-cadherin was downregulated when knocking-down SNHG4 in CRC cells. Conclusions: Our findings demonstrated that SNHG4 played oncogenic roles in CRC, which could be a potential target for treatment of CRC patients, and the results strongly revealed that zebrafish xenograft could be used for functional research of lncRNAs in human cancer.

High-thermopower polarized electrolytes enabled by methylcellulose for low-grade heat harvesting.

Low-grade heat exists ubiquitously in the environment. Thermogalvanic cells (TGCs) are promising for converting the widespread low-grade heat directly into electricity owing to relatively high thermopowers of redox reactions. This work reports polarized electrolytes with ultrahigh thermopowers of -8.18 mV K-1 for n-type and 9.62 mV K-1 for p-type. The electrolyte consists of I-/I3- redox couple, methylcellulose, and KCl. Thermoresponsive methylcellulose leads to polarization switching from n-type to p-type above a transition temperature due to the strong hydrophobic interaction between methylcellulose and I3- ions. The giant thermopowers can be attributed to the simultaneously enhanced entropy change and concentration difference of redox couple enabled by the gelation of methylcellulose and KCl-induced complexation. The p-type TGC with the optimized electrolyte achieves a normalized maximum power density of 0.36 mW m-2 K-2, which is far superior to other reported I-/I3--based TGCs. This work demonstrates cost-effective, high-thermopower polarized electrolytes for low-grade heat harvesting.

Small phenolic and indolic gut-dependent molecules in the primate central nervous system: levels vs. bioactivity.

INTRODUCTION: A rapidly growing body of data documents associations between disease of the brain and small molecules generated by gut-microbiota (GMB). While such metabolites can affect brain function through a variety of mechanisms, the most direct action would be on the central nervous system (CNS) itself. OBJECTIVE: Identify indolic and phenolic GMB-dependent small molecules that reach bioactive concentrations in primate CNS. METHODS: We conducted a PubMed search for metabolomic studies of the primate CNS [brain tissue or cerebrospinal fluid (CSF)] and then selected for phenolic or indolic metabolites that (i) had been quantified, (ii) were GMB-dependent. For each chemical we then conducted a search for studies of bioactivity conducted in vitro in human cells of any kind or in CNS cells from the mouse or rat. RESULTS: 36 metabolites of interests were identified in primate CNS through targeted metabolomics. Quantification was available for 31/36 and in vitro bioactivity for 23/36. The reported CNS range for 8 metabolites 2-(3-hydroxyphenyl)acetic acid, 2-(4-hydroxyphenyl)acetic acid, 3-(3-hydroxyphenyl)propanoic acid, (E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid [caffeic acid], 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2-acetamido-3-(1H-indol-3-yl)propanoic acid [N-acetyltryptophan], 1H-indol-3-yl hydrogen sulfate [indoxyl-3-sulfate] overlapped with a bioactive concentration. However, the number and quality of relevant studies of CNS neurochemistry as well as of bioactivity were highly limited. Structural isomers, multiple metabolites and potential confounders were inadequately considered. CONCLUSION: The potential direct bioactivity of GMB-derived indolic and phenolic molecules on primate CNS remains largely unknown. The field requires additional strategies to identify and prioritize screening of the most promising small molecules that enter the CNS.