Biology subjects

Zhen, L.

Publications and source records attributed to Zhen, L..

8 recordsLinked to original sources

bioRxiv2026

Reducing the Foreign Body Reaction to Neuronal Implants in the Central Nervous System with Porous Precision-templated, Mechanically Compliant Hydrogel Scaffolds

Central nervous system diseases and injuries might be treated by implanted devices, tissue regenerative scaffolds, or drug delivery platforms. However, inflammatory CNS responses limit these interventions and may worsen outcomes following damage to the CNS. Via the foreign body reaction, macrophages and glial cells trigger a "glial scar" around implants, reducing device performance, scaffold regenerative ability, or drug delivery potential. Previous studies have shown that stiffness of CNS implants significantly affects glial encapsulation, but few studies have investigated materials that truly match brain tissue stiffness. Porous precision-templated scaffolds with uniform, interconnected, 40 {micro}m spherical pores have shown favorable healing outcomes and a reduced FBR in numerous soft and hard tissue applications. To quantify the effects of both hydrogel compliance (stiffness) and pore size on glial encapsulation, we implanted poly(2-hydroxyethyl methacrylate-co-glycerol methacrylate) (pHEMA/GMA) scaffolds of varying stiffness and pore size for 4 weeks in rat brain. We observed reduced astrocyte encapsulation around PTS compared to solid hydrogel rods, reduced pro-inflammatory macrophage polarization for softer hydrogels versus stiffer hydrogels, and the presence of new blood vessels, neuronal markers and neurogenesis within the pores. Utilizing soft, precision-porous hydrogels could provide a strategy for mitigating glial scarring and improving regeneration in implant-based CNS treatments.

bioengineering↗

bioRxiv2025

Degraded neural coding of temporal fine structure with age predicts effortful listening in multi-talker environments

Middle age represents a critical window for early detection of neurophysiological decline. Hearing loss is increasingly recognized as both an early marker of neural degeneration and a modifiable risk factor for dementia. Yet many adults report difficulty understanding speech in noise despite normal audiograms, highlighting the limitations of current clinical tests that fail to capture the underlying physiology or effort required for real-world listening. Beyond hearing thresholds, speech comprehension in complex environments depends on precise neural encoding of temporal fine structure (TFS) cues that convey pitch and spatial information. Here, we use a noninvasive EEG-based measure of neural phase-locking (frequency modulation following responses or FMFRs) to quantify TFS encoding in young and middle-aged adults with normal hearing thresholds. Middle-aged listeners exhibited reduced FMFR amplitudes and shallower discriminability slopes, reflecting diminished neural synchrony despite preserved hearing thresholds. Using a multi-talker speech task we further found that pupil-indexed listening effort was significantly greater in middle-aged adults despite matched accuracy across groups. Further, increases in listening effort were predicted by decreases in TFS encoding. Together, these results reveal that degraded neural encoding of TFS underlies subclinical listening difficulties and increased cognitive load, establishing the FMFR as a sensitive biomarker of hidden auditory neural decline. SignificanceUnderstanding speech in noisy environments depends on precise neural encoding of temporal fine structure (TFS) cues. Using a noninvasive EEG metric, the FMFR, we show that neural TFS coding in the peripheral auditory system declines markedly by midlife, even when hearing thresholds and speech performance are normal. These neural deficits predict elevated pupil-indexed listening effort during multi-talker speech perception, revealing that subclinical degradation of temporal coding increases cognitive load in everyday listening. The FMFR thus provides a promising biomarker for early auditory neural decline and its downstream cognitive consequences.

neuroscience↗

bioRxiv2024

Increased listening effort and cochlear neural degeneration underlie behavioral deficits in speech perception in noise in normal hearing middle-aged adults.

Middle age represents a critical period of accelerated brain changes and provides a window for early detection and intervention in age-related neurological decline. Hearing loss is a key early marker of such decline and is linked to numerous comorbidities in older adults. Yet, [~]10% of middle-aged individuals who report hearing difficulties show normal audiograms. Cochlear neural degeneration (CND) could contribute to these hidden hearing deficits, though its role remains unclear due to a lack of objective diagnostics and uncertainty regarding its perceptual outcomes. Here, we employed a cross-species design to examine neural and behavioral signatures of CND. We measured envelope following responses (EFRs) - neural ensemble responses to sound originating from the peripheral auditory pathway - in young and middle-aged adults with normal audiograms and compared these responses to young and middle-aged Mongolian gerbils, where CND was histologically confirmed. We observed near identical changes in EFRs across species that were associated with CND. Behavioral assessments revealed agerelated speech-in-noise deficits under challenging conditions, while pupil-indexed listening effort increased with age even when behavioral performance was matched. Together, these results demonstrate that CND contributes to speech perception difficulties and elevated listening effort in midlife, which may ultimately lead to listening fatigue and social withdrawal.

neuroscience↗

bioRxiv2024

Immunomodulatory Porous Regenerative Scaffolds for in situ Vascular Engineering

The 70-year quest for synthetic vascular graft (sVG) endothelialization has not led to completely healed endothelium in clinically used sVGs. In humans, healing is limited to the vicinity of anastomotic regions (pannus ingrowth) and does not reach the middle regions of sVGs. Here, we conducted proof-of-concept implantation of immunomodulatory porous regenerative scaffolds for in situ vascular engineering (IMPRESSIVE) as interposition grafts in sheep carotid arteries. These scaffolds are based on a new polyurethane (PU) material featuring a 40 {micro}m precision porous structure optimized for angiogenesis. The modulus of the PU was adjusted to match that of natural arteries. The implantation study revealed rapid healing in IMPRESSIVE sVGs. In side-by-side comparison with standard polytetrafluoroethylene (PTFE) grafts, the luminal surfaces of PU grafts were almost completely covered with nucleated cells, while healing in PTFE grafts was limited to several millimeters within anastomotic regions. Endothelialization was observed in the middle regions of PU grafts and overall endothelialization increased significantly compared to PTFE grafts. Densities of mononuclear cells, foreign body giant cells (FBGCs), and endothelial cells within graft walls of PU grafts were also significantly higher than those in PTFE grafts, suggesting transmural cellular infiltration may play a key role in overall improved healing. High percentages of macrophages in pores of PU grafts show Type 1 (CCR7+) and Type 2 (mannose receptor, MR+) characteristics. We also discovered that FBGCs exist in a diverse spectrum of phenotypes. Dually activated FBGCs (CCR7+MR+, G1/2) dominate the population of FBGCs associated with pro-healing PU grafts. These observations suggest a complex, balanced pro-healing response from macrophages and FBGCs. The IMPRESSIVE approach may enable complete endothelialization in pro-healing sVGs and have wide applications in implantable devices and tissue engineering.

bioengineering↗

bioRxiv2023

NULISA: a novel proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range across the proteome. We report a novel proteomic technology - NUcleic acid Linked Immuno-Sandwich Assay (NULISA) - that incorporates a dual capture and release mechanism to suppress the assay background and improves the sensitivity of the proximity ligation assay by over 10,000-fold to the attomolar level. It utilizes pairs of antibodies conjugated to DNA oligonucleotides that enable immunocomplex purification and generate reporter DNA containing target- and sample-specific barcodes for a next-generation sequencing-based, highly multiplexed readout. A 200-plex NULISA targeting 124 cytokines and chemokines and 80 other immune response-related proteins demonstrated superior sensitivity for detecting low-abundance proteins and high concordance with other immunoassays. The ultrahigh sensitivity allowed the detection of previously difficult-to-detect, but biologically important, low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA addresses longstanding challenges in proteomic analysis of liquid biopsies and makes broad and in-depth proteomic analysis accessible to the general research community and future diagnostic applications.

genomics↗

bioRxiv2022

Effect of chemical modifications of tannins on their antibiofilm effect against Gram-negative and Gram-positive bacteria

(1) BackgroundTannins have demonstrated antibacterial and antibiofilm activity, but the mechanisms of action are not completely elucidated. We are interested in understanding how to modulate the antibiofilm activity of tannins and in delineating the relationship between chemical determinants and antibiofilm activity. (2) Materials and methodsthe effect of five different naturally acquired tannins and their chemical derivatives on biofilm formation and planktonic growth of Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was determined in the Calgary biofilm device. (3) Resultsmost of the unmodified tannins exhibited specific antibiofilm activity against the assayed bacteria. The chemical modifications were found to alter the antibiofilm activity level and spectrum of the tannins, with the positive charge introducing C3NMe3Cl-0.5 derivatization shifting the anti-biofilm spectrum towards Gram-negative bacteria and C3NMe3Cl-0.1 and the acidifying CH3COOH derivatization shifting the spectrum towards Gram-positive bacteria. Also, the quantity of phenolic-OH groups per molecule has a weak impact on the anti-biofilm activity of the tannins. (4) Conclusionswe were able to modulate the antibiofilm activity of several tannins by specific chemical modifications, providing a first approach for fine tuning of their activity and spectrum.

microbiology↗

bioRxiv2019

Characterization of Rhodopseudomonas palustris population dynamics on tobacco phyllosphere and induction of plant resistance to Tobacco mosaic virus i

Although many biocontrol bacteria can be used to improve plant tolerance to stresses and to promote plant growth, the hostile environmental conditions on plant phyllosphere and the limited knowledge on bacterial colonization on plant phyllosphere minimized the beneficial effects produced by the biocontrol bacteria. Rhodopseudomonas palustris strain GJ-22 is known as a phyllosphere biocontrol agent. In this paper we described detailed processes of strain GJ-22 colony establishment at various colonization stages. We have shown that the preferable location sites of bacterial aggregates on leaf phyllosphere are grooves between plant epidermal cells. In this study, we categorized bacterial colonies into four phases. Analyses of expressions of plant defense-related genes showed that, starting from Phase III, bacterial cells in the Type 3 and Type 4 colonies started produce unidentified signals to induce host defense again Tobacco mosaic virus infection. To our knowledge, this is the first report focused on the colonization process of a phyllosphere biocontrol agent.

microbiology↗

bioRxiv2018

Mother to child blocking of hepatitis B virus and post vaccination serological test in Qinghai province

BackgroundIn 2016, Qinghai Province and the Asian Liver Center of Stanford University in the United States cooperated to carry out a one-year project of hepatitis B mother-to-child blockade and post-immunization serological test in our province. Through this study, we evaluated the current situation of hepatitis B maternal and infant blockade and the effect of maternal and infant blockade in multi-ethnic areas of Qinghai Province.\n\nMethodsFrom May 1, 2016 to April 30, 2017, all pregnant women who gave birth in Qinghai Province were screened for HBsAg. For pregnant women who were screened for HBsAg positive, the medical staff had a detailed understanding of the history and treatment of hepatitis B, and provided scientific nutritional support and guidance. Free hepatitis B immunoglobulin (100 units) injections were given to newborns born to HBsAg-positive mothers within 12 hours after birth, and three doses of hepatitis B vaccination were given. All newborns born to HBsAg-positive mothers were followed up from 1 to 3 months after complete immunization of HBIG and HepB. The County (district) CDC was responsible for rapid fingertip blood screening, screening for HBsAg-positive children, collecting 3ml of venous blood for quantitative detection of HBsAg.\n\nResultsDuring the study period, 61381 pregnant women were hospitalized, 6027 (97.79%) pregnant women were screened for HBsAg. 1912 pregnant women were detected positive for HBsAg, with a positive rate of 3.19%. The HepB vaccine rate was 97.11% in live infants within 24 hours. The vaccination rate of hepatitis B vaccine was 94.78% and the injection rate of HBIG was 97.15% in 12-hour live delivery children of HBsAg positive mothers. A total of 864 newborns born to HBsAg positive mothers were followed up. Fast fingertip blood test was performed 1-3 months after HBIG injection and whole course hepatitis B vaccination. The positive rate of HBsAg was 5.21%. 34 positive serum samples were detected by chemiluminescent immunoassay in the laboratory of provincial CDC. The coincidence rate of HBsAg positive was 82.35%, and that of HBV DNA positive was 79.41%. Fifty-seven children with HBV surface antibody negative were detected and vaccinated with HBV vaccine free of charge in the whole course according to the national immunization program.\n\nConclusionThe infection rate of hepatitis B among women of childbearing age in Qinghai province is 3.19%, and the blocking rate of mother and infant is 94.79%. It is still necessary to strengthen the injection of hepatitis B vaccine and HBIG for positive mothers and children. Keyword: Hepatitis B, Mother to child blocking, Evaluation of the effect\n\nAuthor SummaryThis study revealed for the first time the infection rate of hepatitis B virus among women of childbearing age of different nationalities in Qinghai-Tibet Plateau through screening of pregnant women in hospital, blocking of mother and infant, and following-up of serum test after immunization. To evaluate the combined blocking effect of hepatitis B vaccine and HBIG by carrying out mother-to-child blocking and follow-up. The results of this study can provide beneficial reference for the development of hepatitis B virus mother-to-child blocking in minority population in Plateau area.

epidemiology↗