A silicon diode-based optoelectronic interface for bidirectional neural modulation.

The development of advanced neural modulation techniques is crucial to neuroscience research and neuroengineering applications. Recently, optical-based, nongenetic modulation approaches have been actively investigated to remotely interrogate the nervous system with high precision. Here, we show that a thin-film, silicon (Si)-based diode device is capable to bidirectionally regulate in vitro and in vivo neural activities upon adjusted illumination. When exposed to high-power and short-pulsed light, the Si diode generates photothermal effects, evoking neuron depolarization and enhancing intracellular calcium dynamics. Conversely, low-power and long-pulsed light on the Si diode hyperpolarizes neurons and reduces calcium activities. Furthermore, the Si diode film mounted on the brain of living mice can activate or suppress cortical activities under varied irradiation conditions. The presented material and device strategies reveal an innovated optoelectronic interface for precise neural modulations.

Multimodal Technologies for Closed-Loop Neural Modulation and Sensing.

Existing methods for studying neural circuits and treating neurological disorders are typically based on physical and chemical cues to manipulate and record neural activities. These approaches often involve predefined, rigid, and unchangeable signal patterns, which cannot be adjusted in real time according to the patient's condition or neural activities. With the continuous development of neural interfaces, conducting in vivo research on adaptive and modifiable treatments for neurological diseases and neural circuits is now possible. In this review, current and potential integration of various modalities to achieve precise, closed-loop modulation, and sensing in neural systems are summarized. Advanced materials, devices, or systems that generate or detect electrical, magnetic, optical, acoustic, or chemical signals are highlighted and utilized to interact with neural cells, tissues, and networks for closed-loop interrogation. Further, the significance of developing closed-loop techniques for diagnostics and treatment of neurological disorders such as epilepsy, depression, rehabilitation of spinal cord injury patients, and exploration of brain neural circuit functionality is elaborated.

Impaired implicit emotion regulation in patients with panic disorder: An event-related potential study on affect labeling.

BACKGROUND: Panic disorder (PD) involves emotion dysregulation, but its underlying mechanisms remain poorly understood. Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance. However, there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators. AIM: To study the neural mechanisms of implicit emotion regulation in PD with event-related potentials (ERP). METHODS: A total of 25 PD patients and 20 healthy controls (HC) underwent clinical eva-luations. The study utilized a case-control design with random sampling, selecting participants for the case group from March to December 2018. Participants performed an affect labeling task, using affect labeling as the experimental condition and gender labeling as the control condition. ERP and behavioral data were recorded to compare the late positive potential (LPP) within and between the groups. RESULTS: Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling. In the HC group, late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease. Importantly, a significant group × condition interaction effect was observed. Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group. Furthermore, among PD patients under the affect labeling, the late LPP was negatively correlated with disease severity, symptom frequency, and intensity. CONCLUSION: PD patients demonstrate abnormalities in implicit emotion regulation, hampering their ability to mobilize cognitive resources for downregulating negative emotions. The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.

The tuber-specific StbHLH93 gene regulates proplastid-to-amyloplast development during stolon swelling in potato.

In potato, stolon swelling is a complex and highly regulated process, and much more work is needed to fully understand the underlying mechanisms. We identified a novel tuber-specific basic helix-loop-helix (bHLH) transcription factor, StbHLH93, based on the high-resolution transcriptome of potato tuber development. StbHLH93 is predominantly expressed in the subapical and perimedullary region of the stolon and developing tubers. Knockdown of StbHLH93 significantly decreased tuber number and size, resulting from suppression of stolon swelling. Furthermore, we found that StbHLH93 directly binds to the plastid protein import system gene TIC56 promoter, activates its expression, and is involved in proplastid-to-amyloplast development during the stolon-to-tuber transition. Knockdown of the target TIC56 gene resulted in similarly problematic amyloplast biogenesis and tuberization. Taken together, StbHLH93 functions in the differentiation of proplastids to regulate stolon swelling. This study highlights the critical role of proplastid-to-amyloplast interconversion during potato tuberization.

Water-Responsive 3D Electronics for Smart Biological Interfaces.

Three-dimensional (3D) electronic systems with their potential for enhanced functionalities often require complex fabrication processes. This paper presents a water-based, stimuli-responsive approach for creating self-assembled 3D electronic systems, particularly suited for biorelated applications. We utilize laser scribing to programmatically shape a water-responsive bilayer, resulting in smart 3D electronic substrates. Control over the deformation direction, actuation time, and surface curvature of rolling structures is achieved by adjusting laser-scribing parameters, as validated through experiments and numerical simulations. Additionally, self-locking structures maintain the integrity of the 3D systems. This methodology enables the implementation of spiral twining electrodes for electrophysiological signal monitoring in plants. Furthermore, the integration of self-rolling electrodes onto peripheral nerves in a rodent model allows for stimulation and recording of in vivo neural activities with excellent biocompatibility. These innovations provide viable paths to next-generation 3D biointegrated electronic systems for life science studies and medical applications.

Ultralow-quantum-defect single-frequency fiber laser.

A single-frequency distributed-Bragg-reflector fiber laser at 980 nm with a quantum defect of less than 0.6% was developed with a 1.5-cm 12 wt% ytterbium-doped phosphate fiber pumped by a 974.5-nm laser diode. Linearly polarized single-longitude-mode laser with a polarization extinction ratio (PER) of nearly 30 dB and spectral linewidth of less than 1.8 kHz was obtained. A maximum output power of 275 mW was measured at a launched pump power of 620 mW. The performance of the single-frequency fiber laser pumped at 909 nm and 976 nm was also characterized. This research demonstrated an approach to high-power single-frequency fiber laser oscillators with mitigated thermal effects.

Preparation, Characterization, and Performance of a Modified Polyacrylamide-Sericite Gel.

In this study, a modified chemical plugging agent is prepared with the aim to reduce the well moisture content and improve the efficiency of oilfield development. In comparison to other chemical plugging agents, the composite gels plugging agents have excellent blocking capacity and erosion resistance. In this study, optimal conditions for the preparation of plugging agents were explored. The results showed that the performance of polyacrylamide-sericite (PAM-sericite) gel improved at a polymerization temperature of 60 °C, a crosslinker concentration of 0.5%, an initiator concentration of 0.75%, an acrylamide concentration of 10.0%, and a sericite concentration of 10.0%. The characterization of PAM-sericite gel showed a certain fold-like shape with a smoother surface, indicating that the doped sericite makes the plugging agent more compact and firm. It was also found that the blocking ratio of the plugging agent can potentially reach 99.5% after the addition of sericite. Moreover, failure stress of the skeleton structure and the water swelling degree were increased by 63.5% and 51.2%, respectively. Additionally, long-term stability, temperature resistance, pressure resistance and pressure stability also showed improvement to varying degrees. It was concluded that this gel has better stability against different kinds of salt solutions and is not affected by particle size.

Effects of Cysticercus cellulosae Excretory-Secretory Antigens on the TGF-ß Signaling Pathway and Th17 Cell Differentiation in Piglets, a Proteomic Analysis.

Excretory-secretory antigens (ESAs) of Cysticercus cellulosae can directly regulate the proliferation and differentiation of host T regulatory (Treg) cells, thus inhibiting host immune responses. However, previous studies have only focused on this phenomenon, and the molecular mechanisms behind the ways in which C. cellulosae ESAs regulate the differentiation of host Treg/Th17 cells have not been reported. We collected CD3+ T cells stimulated by C. cellulosae ESAs through magnetic bead sorting and used label-free quantification (LFQ) proteomics techniques to analyze the signaling pathways of C. cellulosae ESAs regulating Treg/Th17 cell differentiation. Through gene set enrichment analysis (GSEA), we found that C. cellulosae ESAs could upregulate the TGF-ß signaling pathway and downregulate Th17 cell differentiation in piglet T cells. Interestingly, we also found that the IL-2/STAT5 signaling pathway also affects the downregulation of Th17 cell differentiation. C. cellulosae ESAs activate the TGF-ß signaling pathway and the IL-2/STAT5 signaling pathway in host T cells to further regulate the differentiation of Treg/Th17 cells in order to evade host immune attack. This study lays the foundation for the subsequent verification of these pathways, and further clarifies the molecular mechanism of C. cellulosae-mediated immune evasion.

Injection-locked highly Yb3+-doped uncoupled-61-core phosphate fiber laser.

Uncoupled multicore fibers are promising platforms for advanced optical communications, optical computing, and novel laser systems. In this paper, an injection-locked highly ytterbium (Yb3+)-doped uncoupled-61-core phosphate fiber laser at 1030 nm is reported. The 61-core fiber with a core-to-core pitch of 20 µm was fabricated with the stack-and-draw technique. Each core doped with 6-wt.% Yb3+ ions has a diameter of 3 µm and numerical aperture of 0.2. Linearly polarized single-frequency output of 9.1 W was obtained from the injection-locked cavity with a 10-cm-long gain fiber at a pump power of 23.6 W. The injection locking of all 61 cores was confirmed by inspecting the longitudinal modes of the individual lasers with a scanning Fabry-Perot interferometer. The performance of the injection-locked 61-core fiber laser was characterized and compared to that of the free-running operation in terms of optical spectrum, near- and far-field intensity profiles, and relative intensity noise.

Bioresorbable thin-film silicon diodes for the optoelectronic excitation and inhibition of neural activities.

Neural activities can be modulated by leveraging light-responsive nanomaterials as interfaces for exerting photothermal, photoelectrochemical or photocapacitive effects on neurons or neural tissues. Here we show that bioresorbable thin-film monocrystalline silicon pn diodes can be used to optoelectronically excite or inhibit neural activities by establishing polarity-dependent positive or negative photovoltages at the semiconductor/solution interface. Under laser illumination, the silicon-diode optoelectronic interfaces allowed for the deterministic depolarization or hyperpolarization of cultured neurons as well as the upregulated or downregulated intracellular calcium dynamics. The optoelectronic interfaces can also be mounted on nerve tissue to activate or silence neural activities in peripheral and central nervous tissues, as we show in mice with exposed sciatic nerves and somatosensory cortices. Bioresorbable silicon-based optoelectronic thin films that selectively excite or inhibit neural tissue may find advantageous biomedical applicability.

Regulation of piglet T-cell immune responses by thioredoxin peroxidase from Cysticercus cellulosae excretory-secretory antigens.

Taenia solium (T. solium) cysticercosis is a serious threat to human health and animal husbandry. During parasitization, Cysticercus cellulosae (C. cellulosae) can excrete and secrete antigens that modulate the host's T-cell immune responses. However, the composition of C. cellulosae excretory-secretory antigens (ESAs) is complex. This study sought to identify the key molecules in C. cellulosae ESAs involved in regulating T-cell immune responses. Thus, we screened for thioredoxin peroxidase (TPx), with the highest differential expression, as the key target by label-free quantification proteomics of C. cellulosae and its ESAs. In addition, we verified whether TPx protein mainly exists in C. cellulosae ESAs. The TPx recombinant protein was prepared by eukaryotic expression, and ESAs were used as the experimental group to further investigate the effect of TPx protein on the immune response of piglet T cells in vitro. TPx protein induced an increase in CD4+ T cells in piglet peripheral blood mononuclear cells (PBMCs), while CD8+ T cells did not change significantly. This resulted in an imbalance in the CD4+/CD8+ T-cell ratio and an increase in CD4+CD25+Foxp3+ Treg cells in the PBMCs. In addition, TPx protein initiated T helper 2 (Th2)-type immune responses by secreting IL-4 and IL-10 and suppressed Th1/Th17-type immune responses. The results showed that ESAs were involved in regulating piglet T-cell immune responses cells. This suggests that TPx protein found in ESAs plays an essential role to help the parasite evade host immune attack. Moreover, this lays a foundation for the subsequent exploration of the mechanism through which TPx protein regulates signaling molecules to influence T-cell differentiation.

Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe.

Optogenetic methods provide efficient cell-specific modulations, and the ability of simultaneous neural activation and inhibition in the same brain region of freely moving animals is highly desirable. Here we report bidirectional neuronal activity manipulation accomplished by a wireless, dual-color optogenetic probe in synergy with the co-expression of two spectrally distinct opsins (ChrimsonR and stGtACR2) in a rodent model. The flexible probe comprises vertically assembled, thin-film microscale light-emitting diodes with a lateral dimension of 125 × 180 µm2, showing colocalized red and blue emissions and enabling chronic in vivo operations with desirable biocompatibilities. Red or blue irradiations deterministically evoke or silence neurons co-expressing the two opsins. The probe interferes with dopaminergic neurons in the ventral tegmental area of mice, increasing or decreasing dopamine levels. Such bidirectional regulations further generate rewarding and aversive behaviors and interrogate social interactions among multiple mice. These technologies create numerous opportunities and implications for brain research.

A dual-channel optogenetic stimulator selectively modulates distinct defensive behaviors.

Implantable devices and systems have been emerging as powerful tools for neuroscience research and medical applications. Here we report a wireless, dual-channel optoelectronic system for functional optogenetic interrogation of superior colliculus (SC), a layered structure pertinent to defensive behaviors, in rodents. Specifically, a flexible and injectable probe comprises two thin-film microscale light-emitting diodes (micro-LEDs) at different depths, providing spatially resolved optical illuminations within the tissue. Under remote control, these micro-LEDs interrogate the intermediate layer and the deep layer of the SC (ILSC and DLSC) of the same mice, and deterministically evoke distinct freezing and flight behaviors, respectively. Furthermore, the system allows synchronized optical stimulations in both regions, and we discover that the flight response dominates animals' behaviors in our experiments. In addition, c-Fos immunostaining results further elucidate the functional hierarchy of the SC. These demonstrations provide a viable route to unraveling complex brain structures and functions.

Long-term predialysis blood pressure variability and outcomes in hemodialysis patients.

Blood pressure variability (BPV) is significantly associated with cardiovascular diseases (CVD) and mortality in hemodialysis patients. However, the relationship between blood pressure and CVD in hemodialysis patients is complex and affected by many factors. The present study aimed to assess the association of long-term predialysis BPV with all-cause mortality and major adverse cardiovascular events (MACE). One thousand seven hundred twenty-seven patients receiving maintenance hemodialysis were recruited in nine hemodialysis centers. Predialysis BPV was assessed over 1-year intervals. Outcomes included all-cause mortality and MACE during follow-up periods. The mean age of the final cohort was 59 years, of which 57% were males. Greater predialysis systolic BPV was associated with an increased risk of all-cause mortality (adjusted hazard ratio, 1.101; 95% confidence intervals 1.064-1.140) and MACE (adjusted hazard ratio, 1.091; 95% confidence intervals 1.059-1.125). Results were similar when systolic BPV was stratified by baseline systolic blood pressure. In conclusion, greater predialysis BPV among hemodialysis patients was associated with all-cause mortality and MACE. Strategies to reduce blood pressure variability might be beneficial for hemodialysis patients.

Proteomic analysis of Taenia solium cysticercus and adult stages.

Taenia solium (T. solium) cysticercosis is a neglected parasitic zoonosis that occurs in developing countries. Since T. solium has a complex life cycle that includes eggs, oncospheres, cysticerci, and adults, presumably many proteins are produced that enable them to survive and establish an infection within the host. The objectives of this study were to perform a comparative proteomic analysis of two ontogenetic stages of T. solium (cysticerci and adult) and to analyze their differential expression of proteins. Methods proteins were separated by High Performance Liquid Chromatography (HPLC) fractionation, and protein samples were also digested in liquid and identified by liquid chromatography tandem mass spectrometry (LC-MS/MS); the differentially expressed proteins were then processed by a bioinformatics analysis and verified by parallel reaction monitoring (PRM). Results we identified 2,481 proteins by label-free quantitative proteomics. Then differentially expressed proteins were screened under P values < 0.05 and 2 fold change, we found that 293 proteins up-regulated and 265 proteins down-regulated. Discussion through the bioinformatics analysis, we analyzed the differences types and functions of proteins in the Taenia solium and cysticercus, the data will provide reference value for studying the pathogenic mechanism of the two stages and the interaction with the host, and also support for further experimental verification.

Cysticercus cellulosae Regulates T-Cell Responses and Interacts With the Host Immune System by Excreting and Secreting Antigens.

Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4-CD8- T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.

Transfer-printed, tandem microscale light-emitting diodes for full-color displays.

Inorganic semiconductor-based microscale light-emitting diodes (micro-LEDs) have been widely considered the key solution to next-generation, ubiquitous lighting and display systems, with their efficiency, brightness, contrast, stability, and dynamic response superior to liquid crystal or organic-based counterparts. However, the reduction of micro-LED sizes leads to the deteriorated device performance and increased difficulties in manufacturing. Here, we report a tandem device scheme based on stacked red, green, and blue (RGB) micro-LEDs, for the realization of full-color lighting and displays. Thin-film micro-LEDs (size ∼100 µm, thickness ∼5 µm) based on III-V compound semiconductors are vertically assembled via epitaxial liftoff and transfer printing. A thin-film dielectric-based optical filter serves as a wavelength-selective interface for performance enhancement. Furthermore, we prototype arrays of tandem RGB micro-LEDs and demonstrate display capabilities. These materials and device strategies provide a viable path to advanced lighting and display systems.

A wireless, skin-interfaced biosensor for cerebral hemodynamic monitoring in pediatric care.

The standard of clinical care in many pediatric and neonatal neurocritical care units involves continuous monitoring of cerebral hemodynamics using hard-wired devices that physically adhere to the skin and connect to base stations that commonly mount on an adjacent wall or stand. Risks of iatrogenic skin injuries associated with adhesives that bond such systems to the skin and entanglements of the patients and/or the healthcare professionals with the wires can impede clinical procedures and natural movements that are critical to the care, development, and recovery of pediatric patients. This paper presents a wireless, miniaturized, and mechanically soft, flexible device that supports measurements quantitatively comparable to existing clinical standards. The system features a multiphotodiode array and pair of light-emitting diodes for simultaneous monitoring of systemic and cerebral hemodynamics, with ability to measure cerebral oxygenation, heart rate, peripheral oxygenation, and potentially cerebral pulse pressure and vascular tone, through the utilization of multiwavelength reflectance-mode photoplethysmography and functional near-infrared spectroscopy. Monte Carlo optical simulations define the tissue-probing depths for source-detector distances and operating wavelengths of these systems using magnetic resonance images of the head of a representative pediatric patient to define the relevant geometries. Clinical studies on pediatric subjects with and without congenital central hypoventilation syndrome validate the feasibility for using this system in operating hospitals and define its advantages relative to established technologies. This platform has the potential to substantially enhance the quality of pediatric care across a wide range of conditions and use scenarios, not only in advanced hospital settings but also in clinics of lower- and middle-income countries.

Effects of ACEIs and ARBs on the Residual Renal Function in Peritoneal Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In peritoneal dialysis (PD) patients, whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could protect residual renal function is still controversial. To assess the effects of ACEIs and ARBs on the residual renal function and cardiovascular (CV) events in peritoneal dialysis patients, we performed a meta-analysis of randomized controlled trials. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Library, the CNKI database, and the Wanfang database for relevant articles from database inception to November 30, 2019. Randomized controlled trials were included. The primary outcome was the decline in the residual renal function (RRF). RESULTS: Thirteen trials with 625 participants were included in the meta-analysis. The average residual GFR declined by 1.79 ml/min per 1.73 m2 in the ACEI/ARB group versus 1.44 ml/min per 1.73 m2 in the placebo or active control group at 3 mo. The average residual GFR declined by 2.02 versus 2.06, 2.16 versus 2.72, and -0.04 versus 2.74 ml/min per 1.73 m2 in the placebo or active control group at 6 months (mo), 12 mo, and 24 mo, respectively. The decline in residual GFR showed a significant difference between the ACEI/ARB group and the placebo or active control group at 12 mo (MD = -0.64 ml/min per 1.73 m2; 95% CI: -0.97~-0.32; I 2 = 44%; P < 0.0001). No significant difference was observed in Kt/V, urinary protein excretion, weekly creatinine clearance, CV events, or serum potassium levels. CONCLUSIONS: In the present study, we found that the use of ACEIs and ARBs, especially long-term treatment, decreased the decline of RRF in patients on PD. ACEIs and ARBs do not cause an additional risk of side effects.