Tbx2 is a master regulator of inner versus outer hair cell differentiation.

The cochlea uses two types of mechanosensory cell to detect sounds. A single row of inner hair cells (IHCs) synapse onto neurons to transmit sensory information to the brain, and three rows of outer hair cells (OHCs) selectively amplify auditory inputs1. So far, two transcription factors have been implicated in the specific differentiation of OHCs, whereas, to our knowledge, none has been identified in the differentiation of IHCs2-4. One such transcription factor for OHCs, INSM1, acts during a crucial embryonic period to consolidate the OHC fate, preventing OHCs from transdifferentiating into IHCs2. In the absence of INSM1, embryonic OHCs misexpress a core set of IHC-specific genes, which we predict are involved in IHC differentiation. Here we find that one of these genes, Tbx2, is a master regulator of IHC versus OHC differentiation in mice. Ablation of Tbx2 in embryonic IHCs results in their development as OHCs, expressing early OHC markers such as Insm1 and eventually becoming completely mature OHCs in the position of IHCs. Furthermore, Tbx2 is epistatic to Insm1: in the absence of both genes, cochleae generate only OHCs, which suggests that TBX2 is necessary for the abnormal transdifferentiation of INSM1-deficient OHCs into IHCs, as well as for normal IHC differentiation. Ablation of Tbx2 in postnatal, largely differentiated IHCs makes them transdifferentiate directly into OHCs, replacing IHC features with those of mature and not embryonic OHCs. Finally, ectopic expression of Tbx2 in OHCs results in their transdifferentiation into IHCs. Hence, Tbx2 is both necessary and sufficient to make IHCs distinct from OHCs and maintain this difference throughout development.

Prestin's fast motor kinetics is essential for mammalian cochlear amplification.

Prestin (SLC26A5)-mediated voltage-driven elongations and contractions of sensory outer hair cells within the organ of Corti are essential for mammalian cochlear amplification. However, whether this electromotile activity directly contributes on a cycle-by-cycle basis is currently controversial. By restoring motor kinetics in a mouse model expressing a slowed prestin missense variant, this study provides experimental evidence acknowledging the importance of fast motor action to mammalian cochlear amplification. Our results also demonstrate that the point mutation in prestin disrupting anion transport in other proteins of the SLC26 family does not alter cochlear function, suggesting that the potential weak anion transport of prestin is not essential in the mammalian cochlea.

Identifying the protective effects of miR-874-3p/ATF3 axis in intervertebral disc degeneration by single-cell RNA sequencing and validation.

Intervertebral disc degeneration (IVDD) severely affects the work and the quality of life of people. We previously demonstrated that silencing activation transcription factor 3 (ATF3) blocked the IVDD pathological process by regulating nucleus pulposus cell (NPC) ferroptosis, apoptosis, inflammation, and extracellular matrix (ECM) metabolism. Nevertheless, whether miR-874-3p mediated the IVDD pathological process by targeting ATF3 remains unclear. We performed single-cell RNA sequencing (scRNA-seq) and bioinformatics analysis to identify ATF3 as a key ferroptosis gene in IVDD. Then, Western blotting, flow cytometry, ELISA, and animal experiments were performed to validate the roles and regulatory mechanisms of miR-874-3p/ATF3 signalling axis in IVDD. ATF3 was highly expressed in IVDD patients and multiple cell types of IVDD rat, as revealed by scRNA-seq and bioinformatics analysis. GO analysis unveiled the involvement of ATF3 in regulating cell apoptosis and ECM metabolism. Furthermore, we verified that miR-874-3p might protect against IVDD by inhibiting NPC ferroptosis, apoptosis, ECM degradation, and inflammatory response by targeting ATF3. In vivo experiments displayed the protective effect of miR-874-3p/ATF3 axis on IVDD. These findings propose the potential of miR-874-3p and ATF3 as biomarkers of IVDD and suggest that targeting the miR-874-3p/ATF3 axis may be a therapeutic target for IVDD.

The pathogenic roles of the p.R130S prestin variant in DFNB61 hearing loss.

DFNB61 is a recessively inherited nonsyndromic hearing loss caused by mutations in SLC26A5, the gene that encodes the voltage-driven motor protein, prestin. Prestin is abundantly expressed in the auditory outer hair cells that mediate cochlear amplification. Two DFNB61-associated SLC26A5 variants, p.W70X and p.R130S, were identified in patients who are compound heterozygous for these nonsense and missense changes (SLC26A5W70X/R130S ). Our recent study showed that mice homozygous for p.R130S (Slc26a5R130S/R130S ) suffer from hearing loss that is ascribed to significantly reduced motor kinetics of prestin. Given that W70X-prestin is nonfunctional, compound heterozygous Slc26a5R130S/- mice were used as a model for human SLC26A5W70X/R130S . By examining the pathophysiological consequences of p.R130S prestin when it is the sole allele for prestin protein production, we determined that this missense change results in progressive outer hair cell loss in addition to its effects on prestin's motor action. Thus, this study defines the pathogenic roles of p.R130S prestin and identifies a limited time window for potential clinical intervention. KEY POINTS: The voltage-driven motor protein, prestin, is encoded by SLC26A5 and expressed abundantly in cochlear outer hair cells (OHCs). The importance of prestin for normal hearing was demonstrated in mice lacking prestin; however, none of the specific SLC26A5 variants identified to date in human patients has been experimentally demonstrated to be pathogenic. In this study we used both cell lines and a mouse model to define the pathogenic role of compound heterozygous p.W70X (c.209G>A) and p.R130S (c.390A>C) SLC26A5 variants identified in patients with moderate to profound hearing loss. As in patients, mice carrying one copy of p.R130S Slc26a5 showed OHC dysfunction and progressive degeneration, which results in congenital progressive hearing loss. This is the first functional study reporting pathogenic SLC26A5 variants and pointing to the presence of a therapeutic time window for potential clinical interventions targeting the affected OHCs before they are lost.

Rotating twisted templates for imprinting polarization gratings with a sub- to dozen-micron period.

In this Letter, we report and experimentally demonstrate what is to our knowledge a novel scheme for imprinting polarization gratings (PGs) with a pair of templates. Compared with the traditional method that a single template can only imprint PG with a single period, cascading two templates can control the period of imprinted PG at will. However, the low diffraction efficiency is inevitably caused by cascading two templates. Therefore, a rigorous coupled wave analysis (RCWA) is adopted to design a multi-twisted template to address this challenge. As a proof of concept, two multi-twisted templates with a period of 1.6 µm were fabricated, and PGs with a large period range from 0.4 to 48.6 µm were successfully imprinted. The proposed scheme is expected to enable rapid, robust, and high-quality mass production of beam steering, large-angle deflectors, and diffractive optical couplers.

Neural Responses to Auditory Food Stimuli Following Cognitive Behavioral Therapy for Binge-Eating Disorder.

OBJECTIVE: Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC). METHOD: Females with BED (N = 40) were randomized to CBT or WLC. Participants completed assessments at baseline and 16 weeks including measures of eating and appetite and functional magnetic resonance imaging (fMRI) to measure BOLD response while listening to personalized scripts of binge-eating and neutral-relaxing cues. Data were analyzed using general linear models with mixed effects. RESULTS: Overall retention rate was 87.5%. CBT achieved significantly greater reductions in binge-eating episodes than WLC (mean ± standard error decline of 14.6 ± 2.7 vs. 5.7 ± 2.8 episodes in the past 28 days, respectively; p = 0.03). CBT and WLC did not differ significantly in changes in neural responses to binge-eating stimuli during the fMRI sessions. Compared with WLC, CBT had significantly greater improvements in reward-based eating drive, disinhibition, and hunger as assessed by questionnaires (ps < 0.05). DISCUSSION: CBT was effective in reducing binge eating, but, contrary to our hypothesis, CBT did not improve BOLD response to auditory binge-eating stimuli in reward regions of the brain. Further studies are needed to assess mechanisms underlying improvements with CBT for BED. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03604172.

Randomized Controlled Trial of Effects of Behavioral Weight Loss Treatment on Food Cue Reactivity.

BACKGROUND: It is not known whether behavioral weight loss can attenuate blood oxygen level-dependent responses to food stimuli. OBJECTIVES: This randomized controlled trial assessed the effects of a commercially available behavioral weight loss program (WW, WeightWatchers) compared to a wait-list control on blood oxygen level-dependent response to food cues. METHODS: Females with obesity ( N = 61) were randomized to behavioral weight loss or wait-list control. At baseline and follow-up, participants completed assessments that included functional magnetic resonance imaging scans to assess response to images of high-calorie foods (HCF) or low-calorie foods (LCF), and neutral objects. RESULTS: There were no significant between-group differences in change from baseline to follow-up in any regions of the brain in response to viewing HCF or LCF. From baseline to follow-up, participants in behavioral weight loss, compared with wait-list control, reported significantly greater increases in desire for LCF. Changes in liking and palatability of LCF and liking, palatability, and desire for HCF did not differ between groups. DISCUSSION: Behavioral weight loss was associated with increased desire for LCF without changes in neural reactivity to food cues. These results suggest that alteration of neurological processes underlying responsiveness to food is difficult to achieve through behavioral weight management alone.

Super-Transparent Soil for In Situ Observation of Root Phenotypes.

Transparent soil (TS) presents immense potential for root phenotyping due to its ability to facilitate high-resolution imaging. However, challenges related to transparency, mechanical properties, and cost hinder its development. Herein, we introduce super-transparent soil (s-TS) prepared via the droplet method using low acyl gellan gum and hydroxyethyl cellulose crosslinked with magnesium ions. The refractive index of the hydroxyethyl cellulose solution (1.345) closely aligns with that of water (1.333) and the low acyl gellan gum solution (1.340), thereby significantly enhancing the transmittance of hydrogel-based transparent soil. Optimal transmittance (98.45%) is achieved with polymer concentrations ranging from 0.8 to 1.6 wt.% and ion concentrations between 0.01 and 0.09 mol·L-1. After 60 days of plant cultivation, s-TS maintains a transmittance exceeding 89.5%, enabling the detailed visualization of root growth dynamics. Furthermore, s-TS exhibits remarkable mechanical properties, withstanding a maximum compressive stress of 477 kPa and supporting a maximum load-bearing depth of 186 cm. This innovative approach holds promising implications for advanced root phenotyping studies, fostering the investigation of root heterogeneity and the development of selective expression under controlled conditions.

Flexible Zn-ion Electrochromic Batteries with Multiple-color Variations.

Electrochromic batteries as emerging smart energy devices are highly sought after owing to their real-time energy monitoring through visual color conversion. However, their large-scale applicability is hindered by insufficient capacity, inadequate cycling stability, and limited color variation. Herein, a flexible Zn-ion electrochromic battery (ZIEB) was assembled with sodium vanadate (VONa+) cathode, ion-redistributing hydrogel electrolyte, and Zn anode to address these challenges. The electrolyte contains anchored -SO3 - and -NH3 +, which facilitates ionic transportation and prevents Zn dendrite formation by promoting orientated Zn2+ deposition on the Zn (002) surface. The ZIEB exhibits a continuous reversible color transition, ranging from fully charged orange to mid-charged brown and drained green. It also demonstrates a high specific capacity of 302.4 mAh ⋅ g-1 at 0.05 A ⋅ g-1 with a capacity retention of 96.3 % after 500 cycles at 3 A ⋅ g-1. Additionally, the ZIEB maintains stable energy output even under bending, rolling, knotting, and twisting. This work paves a new strategy for the design of smart energy devices in wearable electronics.

SOX8 is essential for male sexual differentiation in the Chinese soft-shelled turtle Pelodiscus sinensis‡.

SOX8, which belongs to SOXE transcription factor subfamily together with SOX9, participates in sex differentiation and testicular development by enhancing the function of SOX9 in mammals. However, the functional role of SOX8 in sex differentiation has not yet been identified in any non-mammalian vertebrates. Here, we found in the Chinese soft-shelled turtle Pelodiscus sinensis that SOX8 exhibited male-specific higher expression from stage 14 to 18, the critical period of sex determination, prior to the onset of gonadal differentiation. In addition, SOX8 was rapidly down-regulated during male-to-female sex reversal induced by estradiol. Moreover, knockdown of SOX8 led to complete feminization of ZZ P. sinensis, determined by gonadal morphology and distribution of germ cells, as well as the down-regulation of testicular marker DMRT1 and the up-regulation of ovarian regulator FOXL2. In conclusion, this study provides evidence that SOX8 is a key regulator of early male differentiation in P. sinensis, highlighting the significance of the SOX family in reptile sex determination.

Geometric-phase-based axicon lens for computational achromatic imaging.

Conventional optical imaging systems usually utilize several lenses within a precise assembly to eliminate chromatic aberration, which increases the difficulty of system integration. In recent years, with the rapid development of metasurfaces and liquid crystals (LCs), planar optical elements provide feasible solutions to realize flexible light manipulation and lightweight systems. However, there also exists chromatic aberration, which can be corrected but at the cost of a complex device design. Here, a geometric-phase-based axicon lens is utilized to correct chromatic aberration across a broadband wavelength with the assistance of a post-process algorithm. The axicon lens is fabricated through arranging orientations of liquid-crystal molecules with a standard photoalignment technique, and it produces an approximately invariant point spread function (PSF) at several discrete wavelengths, which is used as the prior information to extract the object in the blurred image. In the experiment, the reconstruction quality is significantly improved after the post-process algorithm. We expect our work to provide further development to reduce the dispersion with both the device design and the computational image technique.

Selectively reflective edge detection system based on cholesteric liquid crystal: publisher's note.

This publisher's note contains corrections to Opt. Lett.48, 795 (2023)10.1364/OL.481980.

Selectively reflective edge detection system based on cholesteric liquid crystal.

Optical analog computing has attracted extensive interest in image processing and optical engineering in recent decades. Here, we propose a reflective optical analog computing system based on a cholesteric liquid crystal (CLC), which simplifies the traditional optical analog computing system by taking advantage of the CLC reflecting the light with specified circular polarization and provides a new, to the best of our knowledge, idea for the integration of optical analog computing systems. Meanwhile, we present results in which a section of an insect foot is observed using the reflective optical analog computing system, which may develop valuable applications in biomedical imaging.

Simultaneous chiral polarization and edge enhancement imaging enabled by a single geometric-phase-based element.

In this Letter, we propose a multifunctional imaging system enabled by a single geometric-phase-based liquid crystal (LC) element, which integrates chiral polarization and edge enhancement imaging. The element is located at the frequency domain plane in a 4F imaging system, and the phase profile of the element consists of a fork grating in the x direction and a grating in the y direction, which provide edge enhancement and chiral polarization imaging capabilities. Benefiting from the tunable property of the LC, the system can be switched from a polarization and edge imaging mode to the normal conventional imaging mode which is capable of conveniently acquiring the needed image information. Experiments demonstrate that the system can easily achieve multifunctional and switchable imaging, which agrees well with our design, and our LC element can work in the broadband spectrum because of the geometric phase modulation. The multifunctional strategy used here can effectively avoid the need to increase the size of the original microscopic system and the need for additional mechanical rotation of components. We believe that the proposed system with the additional advantages of electric control and tunability can find applications in biological imaging, medical detection, and optical computing.

Investigation of the immune escape mechanism of Treponema pallidum.

BACKGROUND: Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subspecies pallidum (T. pallidum), which is a public health problem that seriously affects human health worldwide. T. pallidum is characterized by early transmission and immune escape and is therefore termed an "invisible pathogen". METHODS: This review systematically summarizes the host's innate and adaptive immune responses to T. pallidum infection as well as the escape mechanisms of T. pallidum. PURPOSE: To lay the foundation for assessing the pathogenic mechanism and the systematic prevention and treatment of syphilis. CONCLUSION: The immune escape mechanism of T. pallidum plays an important role in its survival. Exploring the occurrence and development of these mechanisms has laid the foundation for the development of syphilis vaccine.

Novel Compounds with Promising IDO1 Inhibitory Activity As New Cancer Drug Candidates: Derivatives Of N, N'-diphenylurea Linked With 1,2,3-triazole.

To explore potential indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, we designed a series of compounds incorporating urea and 1,2,3-triazole structures. IDO1 enzymatic activity experiments with the synthesized compounds were used to verify their molecular-level activity; for instance, the half maximal inhibitory concentration value of compound 3c was 0.07 µM. Our research has yielded a series of novel IDO1 inhibitors which may be beneficial in the development of drugs targeting IDO1 for cancer treatment.

Se Ameliorates Cd Toxicity in Oilseed rape (Brassica napus L.) Seedlings by Inhibiting Cd Transporter Genes and Maintaining root Plasma Membrane Integrity.

Se (Selenium) has been reported to be an important protective agent to decreases Cd (Cadmium) induced toxic in plants. However, it remains unclear how Se mitigates the uptake of Cd and increased the resistance to Cd toxicity. Hydroponic experiments were arranged to investigate the changes of physiological properties, root cell membrane integrity and Cd-related transporter genes in rape seedlings. Comparison of the biomass between the addition of Se and the absence of Se under Cd exposure showed that the Cd-induced growth inhibition of rape seedlings was alleviated by Se. Cd decreased the photosynthetic rate (Pn), stomatal conductance (Gs) and photosynthetic pigment content including chlorophyll a, chlorophyll b and carotenoid. However, all these parameters were all significantly improved by Se addition. Moreover, exposure to Se resulted in a decrease in Cd concentration in both shoot and root, ranging from 4.28 to 27.2%. Notably, the application of Se at a concentration of 1 µmol L- 1 exhibited the best performance. Furthermore, Se enhanced cell membrane integrity and reduced superoxide anion levels, thereby contributing to the alleviation of cadmium toxicity in plants. More critically, Se decreased the expression levels of root Cd-related transporter genes BnIRT1, BnHMA2 and BnHMA4 under Cd stress, which are responsible for Cd transport and translocation. These results are important to increase crop growth and reduce Cd load in the food chain from metal toxicity management and agronomical point of view.

Object recognition in optical camera communication enabled by image restoration.

As an important branch of visible light communication (VLC), optical camera communication (OCC) has received increasing attention recently, owing to its availability and low cost of deployment by re-using cameras as VLC receivers. However, cameras on popular smartphones and/or closed-circuit television systems have their primary function for taking pictures and recognizing objects, where the recorded images with objects are inevitable to be distorted by the coded light under OCC. To this end, we propose and experimentally demonstrate an improved OCC system which is able to achieve data communication and object recognition simultaneously. Basically, we devise an image restoration (IR) scheme to repair the pixels damaged by modulated light during data transmission, and it hence provides better image input to realize object recognition. Moreover, to maintain a reasonable data rate of OCC, we also engineer an object avoidance (OA) scheme to remove the negative effect caused by the object background in OCC frame. Finally, we implement a prototype of the proposed system to verify its performance on object recognition and communication, and experimental results show that the proposed IR can bring an improvement over 37% in terms of object recognition accuracy comparing to the baseline under a data rate of 5 kbps.

Enabling Antibacterial and Antifouling Coating via Grafting of a Nitric Oxide-Releasing Ionic Liquid on Silicone Rubber.

Infections caused by bacteria and biofilms on the surfaces of biomedical devices and implants pose serious threats to public health. Herein, a nitric oxide (NO) gas-releasing quaternary ammonium-type ionic liquid (IL)-based coating on polydimethylsiloxane (PDMS), PDIL-NO, with effective and long-acting antibacterial and antifouling properties was prepared. N-(2-((2, 3-Dimethylbut-3-enoyl)oxy)ethyl)-N, N-dimethyloctan-1-aminium bromide (IL-Br), and 2-methyl-2-propenoic acid 2-(2-methoxyethoxy) ethyl ester were covalently grafted onto the surfaces of PDMS by a thiol-ene click chemical reaction, followed by incorporation of l-proline anions (Pro-) through anion exchange with Br- to adsorb NO gas. The prepared PDIL-NO showed a prolonged NO-releasing time (>1440 min) and a relatively high concentration (88 µM). Additionally, PDIL-NO possessed good and long-term antimicrobial activity, and could effectively reduce the adsorption of bovine serum albumin and adhesion of bacteria, as well as inhibit wound infection and reduce inflammation in vivo due to the synergetic effect of IL and the released NO. This study may provide a new approach to combat bacterial infections associated with biomedical devices and implants.

Relationships among Alcohol Drinking Patterns, Macronutrient Composition, and Caloric Intake: National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND: Excessive alcohol consumption is associated with poor diet. Mixed reports in literature, so far, emphasize on the detailed understanding of relationships between diet composition and binge drinking at different drinking thresholds. OBJECTIVE: We examined the association of alcohol consumption thresholds with macronutrient composition, caloric intake and anthropometric measures from the NHANES 2017-2018 dataset. METHODS: A total of 2320 participants' data were analyzed. Energy and nutrient content from daily food and beverage intake were assessed via two dietary recall interviews. Physical examination and Alcohol Use Questionnaire including details about lifetime and current usage patterns were obtained. Correlations were evaluated using the Rao-Scott F Adjusted Chi-square statistic and Wald F-test. Sample-weighted multiple linear regression models were built to analyze the associations among volume of alcohol consumed, weight history and macronutrient intake. RESULTS: Waist circumference was significantly higher in 0- < 4 drinks/episode (low-quantity) drinkers than 4-7 drinks/episode (medium-quantity) and 8-11 drinks/episode (high-quantity) drinkers. High-quantity drinkers consumed significantly more kilocalories (2569.91) compared with low-quantity drinkers (2106.73). Low-quantity drinkers consumed more energy from carbohydrate and fat than medium and high-quantity drinkers. Very high-quantity drinkers (12+ drinks/episode) consumed less fiber (12.81 g) than low-quantity drinkers (16.67 g). CONCLUSIONS: We observed an association between high alcohol intake and differences in eating habits and body composition. The findings suggest a need to compare more specific drinking patterns and their impact on nutrient intake. Although some results conflicted with previous studies, the mechanisms underlying alcohol's effect on ingestive and digestive metabolic pathways are still unclear and require further investigation.