Noninvasive Submillimeter-Precision Brain Stimulation by Optically-Driven Focused Ultrasound

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited millimeter-level precision. Here, we report an optically-driven focused ultrasound (OFUS) for non-invasive brain stimulation with submillimeter precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with a lateral resolution of 83 micrometers, which is two orders of magnitude smaller than that of conventional transcranial focused ultrasound (tFUS). Effective OFUS neurostimulation in vitro with a single ultrasound cycle is shown. Submillimeter transcranial stimulation of mouse motor cortex in vivo is demonstrated. An acoustic energy of 0.02 J/cm^2, two orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. By delivering a submillimeter focus non-invasively, OFUS opens a new way for neuroscience studies and disease treatments.Comment: 36 pages, 5 main figures, 13 supplementary figure

Multiwindow SRS imaging using a rapid widely tunable fiber laser

Spectroscopic stimulated Raman scattering (SRS) imaging has become a useful tool finding a broad range of applications. Yet, wider adoption is hindered by the bulky and environmentally sensitive solid-state optical parametric oscillator (OPO) in a current SRS microscope. Moreover, chemically informative multiwindow SRS imaging across C-H, C-D, and fingerprint Raman regions is challenging due to the slow wavelength tuning speed of the solid-state OPO. In this work, we present a multiwindow SRS imaging system based on a compact and robust fiber laser with rapid and wide tuning capability. To address the relative intensity noise intrinsic to a fiber laser, we implemented autobalanced detection, which enhances the signal-to-noise ratio of stimulated Raman loss imaging by 23 times. We demonstrate high-quality SRS metabolic imaging of fungi, cancer cells, and Caenorhabditis elegans across the C-H, C-D, and fingerprint Raman windows. Our results showcase the potential of the compact multiwindow SRS system for a broad range of applications.R35 GM136223 - NIGMS NIH HHS; R01 AI141439 - NIAID NIH HHS; R01 CA224275 - NCI NIH HHSAccepted manuscrip

Bond-Selective Intensity Diffraction Tomography

Recovering molecular information remains a grand challenge in the widely used holographic and computational imaging technologies. To address this challenge, we developed a computational mid-infrared photothermal microscope, termed Bond-selective Intensity Diffraction Tomography (BS-IDT). Based on a low-cost brightfield microscope with an add-on pulsed light source, BS-IDT recovers both infrared spectra and bond-selective 3D refractive index maps from intensity-only measurements. High-fidelity infrared fingerprint spectra extraction is validated. Volumetric chemical imaging of biological cells is demonstrated at a speed of ~20 seconds per volume, with a lateral and axial resolution of ~350 nm and ~1.1 micron, respectively. BS-IDT's application potential is investigated by chemically quantifying lipids stored in cancer cells and volumetric chemical imaging on Caenorhabditis elegans with a large field of view (~100 micron X 100 micron)

Stakeholder efforts to mitigate antiretroviral therapy interruption among people living with HIV during the COVID-19 pandemic in China: a qualitative study.

INTRODUCTION: The COVID-19 pandemic has affected antiretroviral therapy (ART) continuity among people living with HIV (PLHIV) worldwide. We conducted a qualitative study to explore barriers to ART maintenance and solutions to ART interruption when stringent COVID-19 control measures were implemented in China, from the perspective of PLHIV and relevant key stakeholders. METHODS: Between 11 February and 15 February 2020, we interviewed PLHIV, community-based organization (CBO) workers, staff from centres for disease control and prevention (CDC) at various levels whose work is relevant to HIV care (CDC staff), HIV doctors and nurses and drug vendors from various regions in China. Semi-structured interviews were conducted using a messaging and social media app. Challenges and responses relevant to ART continuity during the COVID-19 pandemic were discussed. Themes were identified by transcript coding and mindmaps. RESULTS: Sixty-four stakeholders were recruited, including 16 PLHIV, 17 CBO workers, 15 CDC staff, 14 HIV doctors and nurses and two drug vendors. Many CDC staff, HIV doctors and nurses responsible for ART delivery and HIV care were shifted to COVID-19 response efforts. Barriers to ART maintenance were (a) travel restrictions, (b) inadequate communication and bureaucratic obstacles, (c) shortage in personnel, (d) privacy concerns, and (e) insufficient ART reserve. CBO helped PLHIV maintain access to ART through five solutions identified from thematic analysis: (a) coordination to refill ART from local CDC clinics or hospitals, (b) delivery of ART by mail, (c) privacy protection measures, (d) mental health counselling, and (e) providing connections to alternative sources of ART. Drug vendors contributed to ART maintenance by selling out-of-pocket ART. CONCLUSIONS: Social and institutional disruption from COVID-19 contributed to increased risk of ART interruption among PLHIV in China. Collaboration among key stakeholders was needed to maintain access to ART, with CBO playing an important role. Other countries facing ART interruption during current or future public health emergencies may learn from the solutions employed in China

Anomalous structural evolution and glassy lattice in mixed-halide hybrid perovskites

Hybrid halide perovskites have emerged as highly promising photovoltaic materials because of their exceptional optoelectronic properties, which are often optimized via compositional engineering like mixing halides. It is well established that hybrid perovskites undergo a series of structural phase transitions as temperature varies. In this work, the authors find that phase transitions are substantially suppressed in mixed-halide hybrid perovskite single crystals of MAPbI3-xBrx (MA = CH3NH3+ and x = 1 or 2) using a complementary suite of diffraction and spectroscopic techniques. Furthermore, as a general behavior, multiple crystallographic phases coexist in mixed-halide perovskites over a wide temperature range, and a slightly distorted monoclinic phase, hitherto unreported for hybrid perovskites, is dominant at temperatures above 100 K. The anomalous structural evolution is correlated with the glassy behavior of organic cations and optical phonons in mixed-halide perovskites. This work demonstrates the complex interplay between composition engineering and lattice dynamics in hybrid perovskites, shedding new light on their unique properties.Peer ReviewedPostprint (published version

Near-infrared anti-microbial therapy: eliminating MRSA by bleaching of STX

Methicillin-resistant Staphylococcus aureus (MRSA) caused invasive infection is a major public health problem primarily related to hospitals or other healthcare settings. However, traditional antibiotics were no longer effective enough because of the ability of pathogens to continuously develop antibiotic resistances. In order to find alternatives in treating MRSA infections, scientists targeted on a goldencolored pigment Staphyloxanthin (STX) located on most of S. aureus membrane, which is one of the virulence factor that help MRSA evade from antibiotic toxicity. Getting rid of STX was proved to sensitize MRSA against drugs including β-lactam antibiotics. Delightfully, both direct inhibition of STX expression and indirect blue light photobleaching of STX were proved to be effective in eradication MRSA in vitro and in vivo. However, protein inhibition took too long time to work, and had off-targeting and cell toxicity issue; and blue light photolysis can hardly be effective into the soft tissue layer of human skin for treating invasive infections because of the limitation in its penetration depth. This thesis illustrates a NIR light illuminating method in STX bleaching, opening a new window for invasive MRSA treatment. According to our results, NIR light was proved to effectively break down STX molecule in a wide range of wavelength, and induce synergistical effect with H2O2 in eradicating planktonic MRSA. H2O2 was to produce reactive oxygen species (ROS) that can disturb the cellular oxidative environment and induce cell death. Moreover, fresh porcine skin was applied to demonstrate the potential penetration depth of NIR laser and STX photolysis effciency through a thick turbid skin tissue. Colony forming unit was conducted to verify the bacterial killing effciency. Resonant Raman spectroscopy was used for quantification of the STX photolysis by characteristic Raman peaks. Different laser systems were applied for particular purposes: femto-second laser with fixed wavelength was used for fast bleaching and power dependent tests, and nano-second laser with tunable wavelength was chosen for wavelength dependent experiments. To illustrate the NIR photo-bleaching mechanism, more mysterious findings were presented which need us to uncover in the future. Considering the host immune response in generateing ROS in defending MRSA infections, in the future, either impairing antioxidant systems or enhancing the endogenous levels of ROS in bacteria could be useful strategies to increase oxidative damage onto pathogens.2022-01-28T00:00:00

A module of multifactor‐mediated dysfunction guides the molecular typing of coronary heart disease

Abstract Background Coronary atherosclerotic heart disease (CHD) is the most common cardiovascular disease and has become a leading cause of death globally. Various molecular typing methods are available for the diagnosis and treatment of tumors. However, molecular typing results are not routinely used for CHD. Methods and Results Aiming to uncover the underlying molecular features of different types of CHD, we screened the differentially expressed genes (DEGs) associated with CHD based on the Gene Expression Omnibus (GEO) data and expanded those with the NCBI‐gene and OMIM databases to finally obtain 2021 DEGs. The weighted gene co‐expression analysis (WGCNA) was performed on the candidate genes, and six distinctive WGCNA modules were identified, two of which were associated with CHD. Moreover, DEGs were mined as key genes for co‐expression based on the module network relationship. Furthermore, the differentially expressed miRNAs in CHD and interactions in the database were mined in the GEO data set to build a multifactor regulatory network of key genes for co‐expression. Based on the network, the CHD samples were further classified into five clusters and we defined FTH1, HCAR3, RGS2, S100A9, and TYROBP as the top genes of the five subgroups. Finally, the mRNA levels of FTH1, S100A9, and TYROBP were found to be significantly increased, while the expression of HCAR3 was decreased in the blood of CHD patients. We did not detect measurable levels of RGS2. Conclusion The screened core clusters of genes may be a target for the diagnosis and treatment of CHD as a molecular typing module

Synthesis and Electroluminescence of a Conjugated Polymer with Thermally Activated Delayed Fluorescence

Synthesis and Electroluminescence of a Conjugated Polymer with Thermally Activated Delayed Fluorescenc

COVID-19 vaccine uptake and hesitancy among HIV-infected men who have sex with men in mainland China: a cross-sectional survey

Background Men who have sex with men (MSM), a population bearing the greatest HIV burden in many countries, may also be vulnerable to COVID-19. COVID-19 vaccines are essential to containing the pandemic. However, vaccine hesitancy may compromise vaccine coverage. We aimed to understand the uptake of COVID-19 vaccine and factors associated with COVID-19 vaccine hesitancy among HIV-infected MSM in mainland China. Methods A cross-sectional online survey among HIV-infected MSM was conducted between 13 and 21 February 2021 in mainland China. Variables including demographics, mental health status, HIV characteristics, and knowledge of and attitudes toward COVID-19 pandemic and COVID-19 vaccine were collected. Chi-square tests and multivariable logistic regression were used to analyze factors associated with COVID-19 vaccine hesitancy. Results A total of 1295 participants were included. The median age was 29.3 years (interquartile range [IQR] 25.2–34.0 years). The uptake of COVID-19 vaccine was 8.7%. Two main reasons for receiving vaccines were “regarded vaccination as self-health protection” (67.3%) and “trust in domestic medical technology” (67.3%). Among participants who did not initiate vaccination, concern about side effects (46.4%) and disclosure of HIV infection (38.6%) were top two reasons, and 47.2% had higher vaccine hesitancy. Men who had with high antiretroviral therapy (ART) adherence (adjusted odds ratio [aOR] 0.53, 95% confidence interval [CI] 0.35–0.80), often (0.26, 0.17–0.40) or sometimes (0.46, 0.31–0.67) paid attention to information about the COVID-19 vaccine, preferred domestic vaccines (0.37, 0.24–0.59), thought the pandemic had moderate (0.58, 0.38–0.90) and moderately severe or severe impact (0.54, 0.38–0.78) on immunity, who were waiting for vaccination programs organized at workplace (0.60, 0.44–0.81) and who were unaware of where to get COVID-19 vaccine (0.61, 0.45–0.82) had lower degree of COVID-19 vaccine hesitancy. Men who were concerned about the efficacy (1.72, 1.16–2.54) and side effects (2.44, 1.78–3.35) had higher degree of COVID-19 vaccine hesitancy. Conclusion COVID-19 vaccine uptake among HIV-infected MSM is still suboptimal. Understanding influencing factors of vaccine hesitancy among this group and making tailored measures to alleviate hesitancy would help improve the coverage of COVID-19 vaccination in this population