Bioengineered skin organoids:from development to applications

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

Ultraconformable Integrated Wireless Charging Micro-Supercapacitor Skin

Conformable and wire-less charging energy storage devices play important roles in enabling the fast development of wearable,non-contact soft electronics.However,current wire-less charging power sources are still restricted by limited flexural angles and fragile connection of components,resulting in the failure expression of performance and constraining their fur-ther applications in health monitoring wearables and moveable artificial limbs.Herein,we present an ultracompatible skin-like integrated wireless charging micro-supercapacitor,which building blocks(including electrolyte,electrode and substrate)are all evaporated by liquid precursor.Owing to the infiltration and permeation of the liquid,each part of the integrated device attached firmly with each other,forming a compact and all-in-one configuration.In addition,benefitting from the controllable volume of electrode solution precursor,the electrode thickness is easily regulated varying from 11.7 to 112.5μm.This prepared thin IWC-MSC skin can fit well with curving human body,and could be wireless charged to store electricity into high capacitive micro-supercapacitors(11.39 F cm-3)of the integrated device.We believe this work will shed light on the construction of skin-attachable electronics and irregular sensing microrobots.

Atmospheric Particulate Matter 2.5(PM_(2.5))Induces Cell Damage and Pruritus in Human Skin

With the accelerated rate of urbanization in recent years,air pollution has become an environmental problem that requires urgent resolution,almost all of the world’s population exposed to pollution on a daily basis.Among the various air pollutants,the excessive dispersion and suspension of particulate matter(PM)in the air.

Nanozyme‑Engineered Hydrogels for Anti‑Inflammation and Skin Regeneration

Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.

Alginate oligosaccharide-mediated butyrate-HIF-1a axis improves skin aging in mice

The“gut-skin”axis has been proved and is considered as a novel therapy for the prevention of skin aging.The antioxidant efficacy of oligomannonic acid(MAOS)makes it an intriguing target for use to improve skin aging.The present study further explored whereby MAOS-mediated gut-skin axis balance prevented skin aging in mice.The data indicated the skin aging phenotypes,oxidative stress,skin mitochondrial dysfunction,and intestinal dysbiosis(especially the butyrate and HIF-1a levels decreased)in aging mice.Similarly,fecal microbiota transplantation(FMT)from aging mice rebuild the aging-like phenotypes.Further,we demonstrated MAOS-mediated colonic butyrate-HIF-1a axis homeostasis promoted the entry of butyrate into the skin,upregulated mitophagy level and ultimately improving skin aging via HDAC3/PHD/HIF-1a/mitophagy loop in skin of mice.Overall,our study offered a better insights of the effectiveness of alginate oligosaccharides(AOS),promised to become a personalized targeted therapeutic agents,on gut-skin axis disorder inducing skin aging.

The Application Progress of Skin Imaging Technology in Psoriasis

Skin imaging technologies such as dermoscopy, high-frequency ultrasound, reflective confocal microscopy and optical coherence tomography are developing rapidly in clinical application. Skin imaging technology can improve clinical diagnosis rate, and its non-invasiveness and repeatability make it occupy an irreplaceable position in clinical diagnosis. With the “booming development” of medical technology, skin imaging technology can improve clinical diagnosis rate. Researchers have made significant advances in assisting clinical diagnosis, prediction, and treatment of disease. This article reviews the application and progress of skin imaging in the diagnosis of psoriasis.

Isotopic dependence of the yield ratios of light fragments from different projectiles and their unified neutron skin thicknesses

The yield ratios of neutron-proton(R(n/p))and^(3)H-^(3)He(R(^(3)H∕^(3)He))with reduced rapidity from 0 to 0.5 were simulated at 50 MeV/u even-even ^(36−56)Ca+^(40)Ca,even-even ^(48−78)Ni+^(58)Ni,and ^(100−139)Sn(every third isotopes)+112 Sn for full reduced impact parameters using the isospin-dependent quantum molecular dynamics(IQMD)model.The neutron and proton density distributions and root-mean-square radii of the reaction systems were obtained using the Skyrme-Hartree-Fock model,which was used for the phase space initialization of the projectile and target in IQMD.We defined the unified neutron skin thickness asΔRnp=<r^(2)>^(1∕2) n−<r^(2)>^(1∕2)p,which was negative for neutron-deficient nuclei.The unifiedΔRnp values for nuclei with the same relative neutron excess from different isotopic chains were nearly equal,except for extreme neutron-rich isotopes,which is a type of scaling behavior.The yield ratios of the three isotopic chain-induced reactions,which depended on the reduced impact parameter and unified neutron skin thickness,were studied.The results showed that both R(n/p)and R(^(3)H∕^(3)He)decreased with a reduced impact parameter for extreme neutron-deficient isotopes;however,they increased with reduced impact parameters for extreme neutron-rich isotopes,and increased with theΔRnp of the projectiles for all reduced impact parameters.In addition,a scaling phenomenon was observed betweenΔR np and the yield ratios in peripheral colli-sions from different isotopic chain projectiles(except for extreme neutron-rich isotopes).Thus,R(n/p)and R(^(3)H∕^(3)He)from peripheral collisions were suggested as experimental probes for extracting the neutron or proton skin thicknesses of non-extreme neutron-rich nuclei from different isotopic chains.

Investigation of the cell composition and gene expression in the delayed-type hypersensitivity tuberculin skin test

Dear Editor,The tuberculin skin test(TST)reagents have continuously improved,with the ESAT6-CFP10(EC)test having recently been introduced,but are seldom based on the direction of the delayed-type hypersensitivity(DTH)mechanism.Previous studies only partially showed the infiltration and activation of immune cells and the production of cytokines of the skin induration[1,2],and lack the detailed measurements of cell proportions and gene expression in the DTH response.Therefore,in this study,we revealed the comprehensive characteristics of DTH by single-cell RNA sequencing(scRNA-seq)in the guinea pig tuberculosis(TB)model[Experimental Animal Welfare Ethics Committee,Beijing Tuberculosis and Thoracic Tumor Research Institute(2021-064)].

Unique Clinical Features of Curaderm when Treating Skin Cancers

Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.

The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment

The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.

Effects of 1-methylcyclopropene on skin greasiness and quality of'Yuluxiang'pear during storage at 20℃

During storage at 20℃,specific pear cultivars may exhibit a greasy texture and decline in quality due to fruit senescence.Among these varieties,‘Yuluxiang’is particularly susceptible to peel greasiness,resulting in significant economic losses.Therefore,there is an urgent need for a preservative that can effectively inhibit the development of greasiness.Previous studies have demonstrated the efficacy of 1-methylcyclopropene(1-MCP)in extending the storage period of fruits.We hypothesize that it may also influence the occurrence of postharvest peel greasiness in the‘Yuluxiang’pears.In this study,we treated‘Yuluxiang’pears with 1-MCP.We stored them at 20℃while analyzing the composition and morphology of the surface waxes,recording enzyme activities related to wax synthesis,and measuring indicators associated with fruit storage quality and physiological characteristics.The results demonstrate that prolonged storage at 20℃leads to a rapid increase in skin greasiness,consistent with the observed elevations in L^(*),greasiness score,and the content of total wax and greasy wax components.Moreover,there were indications that cuticular waxes underwent melting,resulting in the formation of an amorphous structure.In comparison to controls,the application of 1-MCP significantly inhibited increments in L^(*) values as well as grease scores while also reducing accumulation rates for oily waxes throughout most stages over its shelf period,additionally delaying transitions from flaky-wax structures towards their amorphous counterparts.During the initial 7 d of storage,several enzymes involved in the biosynthesis and metabolism of greasy wax components,including lipoxygenase(LOX),phospholipase D(PLD),andβ-ketoacyl-CoA synthase(KCS),exhibited an increase followed by a subsequent decline.The activity of LOX during early shelf life(0–7 d)and the KCS activity during middle to late shelf life(14–21 d)were significantly suppressed by 1-MCP.Additionally,1-MCP effectively maintained firmness,total soluble solid(TSS)and titratable acid(TA)contents,peroxidase(POD),and phenylalanine ammonia-lyase(PAL)activities while inhibiting vitamin C degradation and weight loss.Furthermore,it restrained polyphenol oxidase(PPO)activity,ethylene production,and respiration rate increase.These findings demonstrate that 1-MCP not only delays the onset of peel greasiness but also preserves the overall storage quality of‘Yuluxiang’pear at a temperature of 20℃.This study presents a novel approach for developing new preservatives to inhibit pear fruit peel greasiness and provides a theoretical foundation for further research on pear fruit preservation.

Skin and Soft Tissue Infections in the Surgical Area at the Kara Teaching Hospital

Objective: To report the management of skin and soft tissue infections in the surgical area of Kara University Hospital in Togo. Material and Methods: This study was conducted retrospectively from January 1, 2021, to December 31, 2022, in the general surgery and orthopedic trauma departments. The study focused on soft tissue infections of the pelvic and thoracic limbs and analyzed epidemiological, clinical, paraclinical, therapeutic, and evolutionary data. Results: We registered 165 patients, comprising 109 men and 56 women.The sex ratio (F/H) were 0.51. The mean age was 45 years with extremes ranging from 23 to 90 years. Farmers (64.8%) followed by housewives (34.0%) were the social strata most affected. The consultation period varied between 1 and 90 days. The pathologies found were necrotizing fasciitis (53.3%), erysipelas (18.2%), infected limb wounds (12.1%), pyomyositis (9.7%), and necrotizing dermo-hypodermitis (1.8%). The main procedures performed were necrosectomy and grafting (62.9%), sample necrosectomy (18.8%), drainage (9.7%), and pelvic limb amputation (1.2%). Follow-up was favorable in 86.7% of cases. The study noted a death rate of 13.3% due to septic shock secondary to a delay in consultation. Conclusion: Skin and soft tissue infections were a common reason for surgical hospitalization at Kara University Hospital, with a high mortality rate due to delayed consultations.

Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

Evidence-Based Nursing Practice of Reducing Immune-Related Skin Toxicity of Tumor Patients Guided by Sensitive Indicators

Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.

Clinical efficacy of intradermal type Ⅰ collagen injections in treating skin photoaging in patients from high-altitude areas

BACKGROUND Photoaging,a result of chronic sun exposure,leads to skin damage and pigmentation changes.Traditional treatments may have limitations in high-altitude areas like Yunnan Province.Intradermal Col Ⅰ injections stimulate collagen production,potentially improving skin quality.This study aims to assess the efficacy and safety of this treatment for photoaging.AIM To evaluate the efficacy and safety of intradermal typeΙcollagen(ColΙ)injection for treating photoaging.METHODS This prospective,self-controlled study investigated the impact of intradermal injections of ColΙon skin photodamage in 20 patients from the Yunnan Province.Total six treatment sessions were conducted every 4 wk±3 d.Before and after each treatment,facial skin characteristics were quantified using a VISIA skin detector.Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector.The Face-Q scale was used for subjective evaluation of the treatment effect by the patients.RESULTS The skin thickness of the right cheek consistently increased after each treatment session compared with baseline.The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline.The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions,whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions.The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline(P<0.05).These findings were also supported by skin ultrasound images.The feature count for the red areas and wrinkle feature count decreased following the treatment(P<0.05).VISIA assessments also revealed a decrease in the red areas after treatment.The Face-QSatisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session.The overall appearance of the patients improved after treatment.CONCLUSION Intradermal ColΙinjection improves photoaging,with higher patient satisfaction and fewer adverse reactions,and could be an effective treatment method for populations residing in high-altitude areas.

Dual-Fields Rotational Total Skin Electron Therapy: Investigation and Implementation

Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. Methods and Materials: The DFR-TSET combined the Stanford 6-field and McGill rotational methods. Dual 6 MeV electron beams in high dose total skin electron mode were used for DFR-TSET on a commercial linac. Beam profiles and dosimetric properties were measured using solid phantoms. The dose rate at expanded source-to-surface distance (SSD) was a combination of static rate and rotational rate. In vivo dosimetry of patient skin was performed on patients’ skin using film, metal oxide semiconductor field-effect transistors (MOSFET), and optically stimulated luminescent dosimeters (OSLD). Results: Dual field rotational total skin electron therapy exhibited good (≤±10%) uniformity in the beam profiles in the vertical direction at an extended SSD of 332 cm with a gantry angulation of ±20˚ deviated from the horizontal direction. In-vivo measurements confirmed acceptable uniformity of the patients’ total body surfaces and revealed anatomically self-blocked or shielded areas where underdosing occurred. Conclusions: The clinical implementation of DFR-TSET effectively utilizes the special mode on a linac. This technique provides short beam-on times, uniform dose distribution, large treatment field, and reduced dose of x-ray contamination to the patients. In-vivo measurements indicate satisfactory delivery and dose uniformity of the prescribed dose. Electron boost fields are recommended at normal SSDs to address underdosed areas.

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.

Enhancing Skin Cancer Diagnosis with Deep Learning:A Hybrid CNN-RNN Approach

Skin cancer diagnosis is difficult due to lesion presentation variability. Conventionalmethods struggle to manuallyextract features and capture lesions spatial and temporal variations. This study introduces a deep learning-basedConvolutional and Recurrent Neural Network (CNN-RNN) model with a ResNet-50 architecture which usedas the feature extractor to enhance skin cancer classification. Leveraging synergistic spatial feature extractionand temporal sequence learning, the model demonstrates robust performance on a dataset of 9000 skin lesionphotos from nine cancer types. Using pre-trained ResNet-50 for spatial data extraction and Long Short-TermMemory (LSTM) for temporal dependencies, the model achieves a high average recognition accuracy, surpassingprevious methods. The comprehensive evaluation, including accuracy, precision, recall, and F1-score, underscoresthe model’s competence in categorizing skin cancer types. This research contributes a sophisticated model andvaluable guidance for deep learning-based diagnostics, also this model excels in overcoming spatial and temporalcomplexities, offering a sophisticated solution for dermatological diagnostics research.

Therapeutic approach to emotional reactions accompanied with thermal skin injury–from basic to epidemiological research

In this editorial,we discuss the status of a therapeutic approach to emotional reactions accompanying thermal skin injuries.Burns are considered a major health problem,as well as an economic and social problem,with potentially devastating and life-changing consequences.They affect a wide range of patients with different damage mechanisms,varied depths,and localizations of the burns.The most common are thermal burns,with more than 11 million occurrences annually according to the World Health Organization data.Thermal skin injuries are among the most tragic and catastrophic injuries,almost unsurpassed in terms of severity,morbidity,and mortality,as well as functional,aesthetic,social,economic,and psychological consequences.Burn survivors face stress,anxiety,depression,low self-esteem,body deformity,social isolation,unemployment,financial burden,and family problems.The advances in acute burn care have allowed researchers and physicians to pay more attention to other effects of burns,focusing on psychological consequences in particular.Apart from the significant improvements in routine protocols,it seems useful to take care of psychological disturbances that occur simultaneously but may emerge as the most lasting outcome of those injuries.In that sense,various standards and additional approaches may be involved to achieve overall recovery.

Boulder-induced form roughness and skin shear stresses in a gravel-bed stream

Boulder spacing in mountain rivers and near-wake flow zones within the boulder array is very useful for fish habitat and growth of aquatic organisms.The present study aims to investigate how the boulder array and spacing influence the near-bed flow structures in a gravel-bed stream.Boulders are staggered over a gravel-bed stream with three different inter-boulder spacing namely(a)large(b)medium and(c)small spacing.An acoustic Doppler velocimeter was used for flow measurements in a rectangular channel and the results were compared with those acquired from numerical simulation.The time-averaged velocity profiles at the near-wake flow zones of boulders experience maximum flow retardation which is an outcome of the boulder-induced form roughness.The ratio of velocity differences associated to form and skin roughness and its positive magnitude reveals the dominance of form roughness closest to the boulders.Form roughness computed is 1.75 to 2 times higher than the skin roughness at the near-wake flow region.In particular,the collective immobile boulders placed at different inter-boulder spacings developed high and low bed shear stresses closest to the boulders.The low bed shear stresses characterised by a secondary peak developed at the trough location of the boulders is attributed to the skin shear stress.Further,the spatial averaging of time-averaged flow quantities gives additional impetus to present an improved illustration of fluid shear stresses.The formation of form-induced shear stress is estimated to be 17%to 23%of doubleaveraged Reynolds shear stress and partially compensates for the damping of time-averaged Reynolds shear stress in the interfacial sub-layer.The quadrant analysis of spatial velocity fluctuations depicts that the form-induced shear stresses are dominant in the interfacial sub-layer and have no significance above the gravel-bed surface.