COVID-19: Post infection implications in different age groups, mechanism, diagnosis, effective prevention, treatment, and recommendations.

SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host response to the virus that begins four weeks after initial infection and persists for an undetermined length of time. Chronic effects are more harmful than acute ones thus, this review explored the long-term effects of the virus on various human organs, including the pulmonary, cardiovascular, and neurological, reproductive, gastrointestinal, musculoskeletal, endocrine, and lymphoid systems and found that SARS-CoV-2 adversely affects these organs of older adults. Regarding diagnosis, the RT-PCR is a gold standard method of diagnosing COVID-19; however, it requires specialized equipment and personnel for performing assays and a long time for results production. Therefore, to overcome these limitations, artificial intelligence employed in imaging and microfluidics technologies is the most promising in diagnosing COVID-19. Pharmacological and non-pharmacological strategies are the most effective treatment for reducing the persistent impacts of COVID-19 by providing immunity to post-COVID-19 patients by reducing cytokine release syndrome, improving the T cell response, and increasing the circulation of activated natural killer and CD8 T cells in blood and tissues, which ultimately reduces fever, nausea, fatigue, and muscle weakness and pain. Vaccines such as inactivated viral, live attenuated viral, protein subunit, viral vectored, mRNA, DNA, or nanoparticle vaccines significantly reduce the adverse long-term virus effects in post-COVID-19 patients; however, no vaccine was reported to provide lifetime protection against COVID-19; consequently, protective measures such as physical separation, mask use, and hand cleansing are promising strategies. This review provides a comprehensive knowledge of the persistent effects of COVID-19 on people of varying ages, as well as diagnosis, treatment, vaccination, and future preventative measures against the spread of SARS-CoV-2.

Hybrid Microneedle-Mediated Transdermal Delivery of Atorvastatin Calcium-Loaded Polymeric Micelles for Hyperlipidemia Therapy.

Hyperlipidemia has been a huge challenge to global health, leading to the cardiovascular disease, hypertension, and diabetes. Atorvastatin calcium (AC), a widely prescribed drug for hyperlipidemia, faces huge challenges with oral administration due to poor water solubility and hepatic first-pass effects, resulting in low therapeutic efficacy. In this work, we designed and developed a hybrid microneedle (MN) patch system constructed with soluble poly(vinyl alcohol) (PVA) and AC-loaded polymeric micelles (AC@PMs) for transdermal delivery of AC to enhance the hyperlipidemia therapy. We first prepared various AC@PM formulations self-assembled from mPEG-PLA and mPEG-PLA-PEG block copolymers using a dialysis method and evaluated the physicochemical properties in combination with experiment skills and dissipative particle dynamics (DPD) simulations. Then, we encapsulated the AC@PMs into the PVA MN patch using a micromold filling method, followed by characterizing the performances, especially the structural stability, mechanical performance, and biosafety. After conducting in vivo experiments using a hyperlipidemic rat model, our findings revealed that the hybrid microneedle-mediated administration exhibited superior therapeutic efficacy when compared to oral delivery methods. In summary, we have successfully developed a hybrid microneedle (MN) patch system that holds promising potential for the efficient transdermal delivery of hydrophobic drugs.

Effect of a fall within three months of admission on delirium in critically Ill elderly patients: a population-based cohort study.

BACKGROUND: Delirium is common among elderly patients in the intensive care unit (ICU) and is associated with prolonged hospitalization, increased healthcare costs, and increased risk of death. Understanding the potential risk factors and early prevention of delirium is critical to facilitate timely intervention that may reverse or mitigate the harmful consequences of delirium. AIM: To clarify the effects of pre-admission falls on ICU outcomes, primarily delirium, and secondarily pressure injuries and urinary tract infections. METHODS: The study relied on data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Statistical tests (Wilcoxon rank-sum or chi-squared) compared cohort characteristics. Logistic regression was employed to investigate the association between a history of falls and delirium, as well as secondary outcomes, while Kaplan-Meier survival curves were used to assess short-term survival in delirium and non-delirium patients. RESULTS: Study encompassed 22,547 participants. Delirium incidence was 40%, significantly higher in patients with a history of falls (54.4% vs. 34.5%, p < 0.001). Logistic regression, controlling for confounders, not only confirmed that a history of falls elevates the odds of delirium (OR: 2.11; 95% CI: 1.97-2.26; p < 0.001) but also showed it increases the incidence of urinary tract infections (OR:1.50; 95% CI:1.40-1.62; p < 0.001) and pressure injuries (OR:1.36; 95% CI:1.26-1.47; p < 0.001). Elderly delirium patients exhibited lower 30-, 180-, and 360-day survival rates than non-delirium counterparts (all p < 0.001). CONCLUSIONS: The study reveals that history of falls significantly heighten the risk of delirium and other adverse outcomes in elderly ICU patients, leading to decreased short-term survival rates. This emphasizes the critical need for early interventions and could inform future strategies to manage and prevent these conditions in ICU settings.

Unleashing the potential of tungsten disulfide: Current trends in biosensing and nanomedicine applications.

The discovery of graphene ignites a great deal of interest in the research and advancement of two-dimensional (2D) layered materials. Within it, semiconducting transition metal dichalcogenides (TMDCs) are highly regarded due to their exceptional electrical and optoelectronic properties. Tungsten disulfide (WS2) is a TMDC with intriguing properties, such as biocompatibility, tunable bandgap, and outstanding photoelectric characteristics. These features make it a potential candidate for chemical sensing, biosensing, and tumor therapy. Despite the numerous reviews on the synthesis and application of TMDCs in the biomedical field, no comprehensive study still summarizes and unifies the research trends of WS2 from synthesis to biomedical applications. Therefore, this review aims to present a complete and thorough analysis of the current research trends in WS2 across several biomedical domains, including biosensing and nanomedicine, covering antibacterial applications, tissue engineering, drug delivery, and anticancer treatments. Finally, this review also discusses the potential opportunities and obstacles associated with WS2 to deliver a new outlook for advancing its progress in biomedical research.

Prompt-enhanced hierarchical transformer elevating cardiopulmonary resuscitation instruction via temporal action segmentation.

The vast majority of people who suffer unexpected cardiac arrest are performed cardiopulmonary resuscitation (CPR) by passersby in a desperate attempt to restore life, but endeavors turn out to be fruitless on account of disqualification. Fortunately, many pieces of research manifest that disciplined training will help to elevate the success rate of resuscitation, which constantly desires a seamless combination of novel techniques to yield further advancement. To this end, we collect a specialized CPR video dataset in which trainees make efforts to behave resuscitation on mannequins independently in adherence to approved guidelines, promoting an auxiliary toolbox to assist supervision and rectification of intermediate potential issues via modern deep learning methodologies. Our research empirically views this problem as a temporal action segmentation (TAS) task in computer vision, which aims to segment an untrimmed video at a frame-wise level. Here, we propose a Prompt-enhanced hierarchical Transformer (PhiTrans) that integrates three indispensable modules, including a textual prompt-based Video Features Extractor (VFE), a transformer-based Action Segmentation Executor (ASE), and a regression-based Prediction Refinement Calibrator (PRC). The backbone preferentially derives from applications in three approved public datasets (GTEA, 50Salads, and Breakfast) collected for TAS tasks, which experimentally facilitates the model excavation on the CPR dataset. In general, we probe into a feasible pipeline that elevates the CPR instruction qualification via action segmentation equipped with novel deep learning techniques. Associated experiments on the CPR dataset advocate our resolution with surpassing 91.0% on Accuracy, Edit score, and F1 score.

Interaction effect of midday napping duration and depressive symptoms on subjective memory impairment among older people in China: evidence from the China health and retirement longitudinal study database.

BACKGROUND: Subjective memory impairment (SMI) is common in older people. The aim of this study was to investigate the factors influencing SMI among older people in China, with specific focus on the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. METHODS: Using a dataset representative of the Chinese population from a longitudinal study of health and retirement in China, subjects with SMI were screened using the question "how do you feel about your memory now?" and the Mini-Mental State Examination. A logistic regression model was applied to explore the factors affecting SMI. Additive and multiplicative models were used to analyze the interaction effect of midday napping duration and depressive symptoms on the risk of SMI. RESULTS: We enrolled 8,254 subjects included and the incidence of SMI was 63.9%. Depressive symptoms, nap time, and physical activity were influencing factors of SMI. Midday napping duration and depressive symptoms had positive additive interaction effects on the risk of SMI. When extended-length naps and depressive symptoms coexisted, the risk of SMI was 1.06 times greater than that for either alone (RERI, relative excess risk due to interaction = 0.27, 95% CI = 0.07-0.43; AP, attributable proportion = 0.14, 95% CI = 0.01-0.23; S, synergy index = 1.06, 95% CI = 0.57-1.62). When short naps and depressive symptoms coexisted, the risk of SMI was 1.2 times higher than that for either alone (RERI = 0.12, 95% CI=-0.14-0.39; AP = 0.13, 95% CI=-0.07-0.22; S = 1.20, 95% CI = 0.79-1.82). LIMITATIONS: Since this was a cross-sectional study, the cause-and-effect relationships between the associated variables cannot be inferred. CONCLUSIONS: The interaction effect that exists between nap time and depressive symptoms in older people is important for the identification and early intervention of people at risk for SMI.

Toxicity mechanism of peri-implantation pesticide beta-cypermethrin exposure on endometrial remodeling in early pregnant mice.

Beta-cypermethrin (ß-CYP) is a universally used pyrethroid pesticide with adverse effects on human health. ß-CYP may impair endometrial remodeling in mice; however, the mechanism remains largely unknown. Endometrial remodeling plays a vital role in embryonic development and the maintenance of pregnancy. Therefore, we explored the mechanism by which peri-implantation ß-CYP administration reduces uterine remodeling in pregnant mice. The C57BL/6 J pregnant mice were administered a dose of 20 mg/kg.bw. d ß-CYP via oral gavage once daily from day 1 of gestation (GD1) to GD7. Molecular markers of endometrial remodeling, stromal cell proliferation, cell cycle regulation, and the PI3K/Akt/mTOR signaling pathway were evaluated in the decidual tissue of the uterus on GD7. An in vivo pseudopregnancy mouse model, a pregnant mouse model treated with an mTOR activator and an mTOR inhibitor and an in vitro decidualization model of mouse endometrial stromal cells were used to confirm ß-CYP-induced defective endometrial remodeling and the key molecules expression of PI3K/Akt/mTOR signaling pathway. The results showed that ß-CYP decreased the expression of the endometrial remodeling markers MMP9 and LIF in the uterine decidua. Peri-implantation ß-CYP treatment markedly downregulated the expression of endometrial proliferation markers PCNA and Ki67 and decreased decidua thickness. Correspondingly, peri-implantation ß-CYP exposure upregulated the expression of FOXO1, P57 and p-4E-BP1 in the decidua. Further experiments showed ß-CYP significantly inhibited key molecules in the PI3K/Akt/mTOR pathway: PI3K, p-Akt/Akt, p-mTOR, and p-P70S6K in the uterine decidua. Additional experiments showed that aberrant endometrial remodeling induced by ß-CYP was aggravated by rapamycin (an mTOR inhibitor) and partially reversed by MHY1485 (an mTOR agonist). In summary, our results indicated that a reduction in the PI3K/Akt/mTOR pathway may enhance defective endometrial remodeling by downregulating the proliferation and differentiation of endometrial stromal cells in early pregnant mice exposed to ß-CYP. Our study elucidates the mechanism of defective endometrial remodeling induced by peri-implantation ß-CYP exposure.

Mining and Validation of Novel Hemp Seed-Derived DPP-IV-Inhibiting Peptides Using a Combination of Multi-omics and Molecular Docking.

Hemp seed-derived inhibitors of dipeptidyl peptidase IV (DPP-IV) demonstrate potential as novel therapeutics for diabetes; however, their proteome and genome remain uncharacterized. We used multi-omics technology to mine peptides capable of inhibiting DPP-IV. First, 1261 and 1184 proteins were identified in fresh and dry hemp seeds, respectively. Simulated protease cleavage of dry seed proteins yielded 185,446 peptides for virtual screening to select the potential DPP-IV-inhibiting peptides. Sixteen novel peptides were selected according to their DPP-IV-binding affinity determined via molecular docking. In vitro DPP-IV inhibition assays identified the peptides LPQNIPPL, YPYY, YPW, LPYPY, WWW, YPY, YPF, and WS with half-maximal inhibitory concentration (IC50) values lower than 0.5 mM, which were 0.08 ± 0.01, 0.18 ± 0.03, 0.18 ± 0.01, 0.20 ± 0.03, 0.22 ± 0.03, 0.29 ± 0.02, 0.42 ± 0.03, and 0.44 ± 0.09 mM, respectively. The dissociation constants (KD) of the 16 peptides ranged from 1.50 × 10-4 to 1.82 × 10-7 M. Furthermore, Caco2 and INS-1 cell assays showed that all 16 peptides could efficiently inhibit DPP-IV activity and increase insulin and glucagon-like peptide-1 concentrations. These results demonstrate a well-established and efficient method to isolate food-derived therapeutic DPP-IV-inhibiting peptides.

Emergence, phylogeography, and adaptive evolution of mpox virus.

Mpox (Monkeypox) is a zoonotic disease caused by mpox virus (MPXV). A multi-country MPXV outbreak in non-endemic demographics was identified in May 2022. A systematic evaluation of MPXV evolutionary trajectory and genetic diversity could be a timely addition to the MPXV diagnostics and prophylaxis. Herein, we integrated a systematic evolution analysis including phylogenomic and phylogeographic, followed by an in-depth analysis of the adaptive evolution and amino acid variations in type I interferon binding protein (IFNα/ßBP). Mutations in IFNα/ßBP protein may impair its binding capacity, affecting the MPXV immune evasion strategy. Based on the equilibrated data, we found an evolutionary rate of 7.75 × 10 - 5 substitutions/site/year, and an earlier original time (2021.25) of the clade IIb. We further discovered significant genetic variations in MPXV genomes from different regions and obtained six plausible spread trajectories from its intricate viral flow network, implying that North America might have acted as a bridge for the spread of MPXV from Africa to other continents. We identified two amino acids under positive selection in the Rifampicin resistance protein and extracellular enveloped virus (EEV) type-I membrane glycoprotein, indicating a role in adaptive evolution. Our research sheds light on the emergence, dispersal, and adaptive evolution of MPXV, providing theoretical support for mitigating and containing its expansion.

Living Leukocyte-Based Drug Delivery Systems.

Leukocytes play a vital role in immune responses, including defending against invasive pathogens, reconstructing impaired tissue, and maintaining immune homeostasis. When the immune system is activated in vivo, leukocytes accomplish a series of orderly and complex regulatory processes. While cancer and inflammation-related diseases like sepsis are critical medical difficulties plaguing humankind around the world, leukocytes have been shown to largely gather at the focal site, and significantly contribute to inflammation and cancer progression. Therefore, the living leukocyte-based drug delivery systems have attracted considerable attention in recent years due to the innate and specific targeting effect, low immunogenicity, improved therapeutic efficacy, and low reverse effect. In this review, the recent advances in the development of living leukocyte-based drug delivery systems including macrophages, neutrophils, and lymphocytes as promising treatment strategies for cancer and inflammation-related diseases are introduced. The advantages, current challenges, and limitations of these delivery systems are also discussed, as well as perspectives on the future development of precision and targeted therapy in the clinics are provided. Collectively, it is expected that such kind of living cell-based drug delivery system is promising to improve or even revolutionize the treatments of cancers and inflammation-related diseases in the clinics.

A comparative study for the effect of different premixed charge ratios with conventional diesel engines on the performance, emissions, and vibrations of the engine block.

Exploratory research of partially premixed charge compression ignition (PCCI) in conjunction with direct fuel injection was done. A single-cylinder commercial diesel engine was used. In this work, the evaluation of the engine vibrations, pollution, efficiency, and combustion properties has been performed on a PCCI diesel-fueled engine. A part of the fuel was converted into vapor inside the intake manifold by using an innovative premixing chamber with an electronic fuel injector. At the same time, the main fuel quantity was injected directly inside the engine cylinder before the top dead center (TDC) to control the engine phasing. A unique approach based on the fast Fourier transform (FFT) of the cylinder vibration data was applied for combustion vibrations and acoustic investigation. To further clarify their relationship, the influence of combustion characteristics on acoustic and vibrations metrics was investigated. The results demonstrate that combustion noise remains a crucial issue for adopting this novel combustion approach in the automotive industry. The studies revealed that partial premixing reduces nitrogen oxide (NOX) pollutants significantly. This is thought to be the outcome of the PCCI combustion, which occurs before the typical mixing controlled phase, lowering regional gas temperatures. The experiment findings also revealed that partial premixing has an intrinsic tradeoff between NOX emissions and inefficient combustion products (carbon monoxide (CO) and unburned hydrocarbons (UHCs)). It was also shown that incomplete combustion and non-optimized spontaneously igniting of the premixed charge resulted in a minor reduction in combustion efficiency (CE).

A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

The Short-term Effectiveness of Three Manipulations for Atlantoaxial Joint Disorders and the Effects on Surface Electromyography of Sternocleidomastoid Muscle / 中医杂志

ObjectiveTo compare the short-term effectiveness of the three different manipulations for atlantoaxial joint disorders and their effects on surface electromyography of sternocleidomastoid muscle. MethodsNinty patients with atlantoaxial joint disorders were randomly divided into the tendon relaxing manipulation group， the tendon relaxing plus rehabilitation manipulation group， and the conventional manipulation group， with 30 cases in each group， and each group of patients received the corresponding manipulation treatment for 2 weeks. The changes of visual analogue score （VAS） of occipital neck pain， evaluation scale for cervical vertigo （ESCV）， and averaged electromyography （AEMG） of surface electromyography of bilateral sternocleidomastoid muscles before and after the treatment were observed， and the clinical effectiveness and safety of the patients were compared among groups. ResultsThe VAS scores of patients in each group decreased， and the ESCV scores increased after treatment （P＜0.01）， and the tendon relaxing manipulation group and the tendon relaxing plus rehabilitation manipulation group were significantly better than the conventional manipulation group （P＜0.01）. The AEMG of the bilateral sternocleidomastoid muscles of the three groups increased after treatment （P＜0.01）； when compared among the three groups， the AEMG of the bilateral sternocleidomastoid muscles of the tendon relaxing plus rehabilitation manipulation group was higher than that of the tendon relaxing manipulation group， and the tendon relaxing manipulation group was higher than that of the conventional manipulation group （P＜0.05 or P＜0.01）. The cure and markedly effective rates of the tendon relaxing manipulation group， the tendon relaxing plus rehabilitation manipulation group， and the conventional manipulation group were 56.67%， 86.67%， and 36.67% respectively， showing statistically difference （K=10.21， P＜0.01）. ConclusionThe tendon relaxing manipulation and tendon relaxing plus rehabilitation manipulation can effectively improve the symptoms of vertigo， headache， and neck pain for patients with atlantoaxial joint disorders， and can improve the contraction function of sternocleidomastoid muscle， whose effectiveness are better than that of conventional manipulation.

Angiotensin-Converting Enzyme 2-Based Biosensing Modalities and Devices for Coronavirus Detection.

Rapid and cost-effective diagnostic tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a critical and valuable weapon for the coronavirus disease 2019 (COVID-19) pandemic response. SARS-CoV-2 invasion is primarily mediated by human angiotensin-converting enzyme 2 (hACE2). Recent developments in ACE2-based SARS-CoV-2 detection modalities accentuate the potential of this natural host-virus interaction for developing point-of-care (POC) COVID-19 diagnostic systems. Although research on harnessing ACE2 for SARS-CoV-2 detection is in its infancy, some interesting biosensing devices have been developed, showing the commercial viability of this intriguing new approach. The exquisite performance of the reported ACE2-based COVID-19 biosensors provides opportunities for researchers to develop rapid detection tools suitable for virus detection at points of entry, workplaces, or congregate scenarios in order to effectively implement pandemic control and management plans. However, to be considered as an emerging approach, the rationale for ACE2-based biosensing needs to be critically and comprehensively surveyed and discussed. Herein, we review the recent status of ACE2-based detection methods, the signal transduction principles in ACE2 biosensors and the development trend in the future. We discuss the challenges to development of ACE2-biosensors and delineate prospects for their use, along with recommended solutions and suggestions.

Knockdown of Bcl-3 alleviates psoriasis and dyslipidemia comorbidity by regulating Akt pathway

Background Psoriasis is considered as an inflammatory skin disease accompanied by dyslipidemia comorbidity. B-cell leukemia-3 (Bcl-3) belongs to IκB (inhibitor of nuclear factor kappa B [NF-κB]) family, and regulates inflammatory response through associating with NF-κB. The role of Bcl-3 in psoriasis was investigated in this study. Methods Apolipoprotein E (ApoE)-deficient mice were treated with imiquimod to induce psoriasis and dyslipidemia. Mice were injected intradermally in the back with lentiviral particles encoding Bcl-3 small hairpin RNA (shRNA). Hematoxylin and eosin were used to detect pathological characteristics. The blood lipid levels were determined by automatic biochemical analyzer, and inflammation was assessed by enzyme-linked-immunosorbent serologic assay and real-time quantitative reverse transcription polymerase chain reaction. Results Bcl-3 was elevated in imiquimod-induced ApoE-deficient mice. Injection with lentiviral particles encoding Bcl-3 shRNA reduced Psoriasis area and severity index (PASI) score in ApoE-deficient psoriatic mice. Knockdown of Bcl-3 also ameliorated imiquimod-induced psoriasiform skin lesions in ApoE-deficient mice. Moreover, loss of Bcl-3 enhanced expression of loricrin, an epidermal barrier protein, reduced expression of proliferating cell nuclear antigen (PCNA) and lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1) in imiquimod-induced ApoE-deficient mice. The enhanced levels of blood lipid in ApoE-deficient mice were attenuated by silencing of Bcl-3 with increase of high-density lipoprotein, and reduction of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Knockdown of Bcl-3 attenuated imiquimod-induced decrease of transforming growth factor beta (TGF-β), and increase of Interleukin (IL)-17A, IL-23, IL-6, and tumor necrosis factor-α (TNF-α) in ApoE-deficient mice. Protein expression of phospho-Akt (p-Akt) and p-GSK3β in ApoE-deficient psoriatic mice was decreased by silencing of Bcl-3 (AU)

Current and Perspective Sensing Methods for Monkeypox Virus.

The outbreak of the monkeypox virus (MPXV) in non-endemic countries is an emerging global health threat and may have an economic impact if proactive actions are not taken. As shown by the COVID-19 pandemic, rapid, accurate, and cost-effective virus detection techniques play a pivotal role in disease diagnosis and control. Considering the sudden multicountry MPXV outbreak, a critical evaluation of the MPXV detection approaches would be a timely addition to the endeavors in progress for MPXV control and prevention. Herein, we evaluate the current MPXV detection methods, discuss their pros and cons, and provide recommended solutions to the problems. We review the traditional and emerging nucleic acid detection approaches, immunodiagnostics, whole-particle detection, and imaging-based MPXV detection techniques. The insights provided in this article will help researchers to develop novel techniques for the diagnosis of MPXV.

RCMNet: A deep learning model assists CAR-T therapy for leukemia.

Acute leukemia is a type of blood cancer with a high mortality rate. Current therapeutic methods include bone marrow transplantation, supportive therapy, and chemotherapy. Although a satisfactory remission of the disease can be achieved, the risk of recurrence is still high. Therefore, novel treatments are demanding. Chimeric antigen receptor-T (CAR-T) therapy has emerged as a promising approach to treating and curing acute leukemia. To harness the therapeutic potential of CAR-T cell therapy for blood diseases, reliable cell morphological identification is crucial. Nevertheless, the identification of CAR-T cells is a big challenge posed by their phenotypic similarity with other blood cells. To address this substantial clinical challenge, herein we first construct a CAR-T dataset with 500 original microscopy images after staining. Following that, we create a novel integrated model called RCMNet (ResNet18 with Convolutional Block Attention Module and Multi-Head Self-Attention) that combines the convolutional neural network (CNN) and Transformer. The model shows 99.63% top-1 accuracy on the public dataset. Compared with previous reports, our model obtains satisfactory results for image classification. Although testing on the CAR-T cell dataset, a decent performance is observed, which is attributed to the limited size of the dataset. Transfer learning is adapted for RCMNet and a maximum of 83.36% accuracy is achieved, which is higher than that of other state-of-the-art models. This study evaluates the effectiveness of RCMNet on a big public dataset and translates it to a clinical dataset for diagnostic applications.

An update on biomaterials as microneedle matrixes for biomedical applications.

Microneedles (MNs) have been developed for various applications such as drug delivery, cosmetics, diagnosis, and biosensing. To meet the requirements of MNs used in these areas, numerous materials have been used for the fabrication of MNs. However, MNs will be exposed to skin tissues after piercing the stratum corneum barrier. Thus, it is necessary to ensure that the matrix materials of MNs have the characteristics of low toxicity, good biocompatibility, biodegradability, and sufficient mechanical properties for clinical application. In this review, the matrix materials currently used for preparing MNs are summarized and reviewed in terms of these factors. In addition, MN products used on the market and their applications are summarized in the end. This work may provide some basic information to researchers in the selection of MN matrix materials and in developing new materials.

Conductive Microneedle Patch with Electricity-Triggered Drug Release Performance for Atopic Dermatitis Treatment.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects the life quality of patients. Topical administration of glucocorticoids is considered to be the most effective anti-inflammatory treatment. However, due to the barrier function of skin, only less than 20% of topical drug molecules could diffuse into the skin. Therefore, it is of great importance to develop an effective strategy to improve AD therapy. In this study, we reported a two-electrode microneedle patch (t-EMNP) composed of a polylactic acid-platinum (PLA-Pt) MN array and polylactic acid-platinum-polypyrrole (PLA-Pt-PPy) MN array for improving the transdermal drug delivery efficacy. The drug loading capability of MNs could be altered by employing different polymerization times and drug concentrations. The drug release rate of MNs could be changed by applying different voltages. We further developed a controlled transdermal drug delivery system (c-TDDS) based on this two-electrode microneedle patch (t-EMNP), exhibiting the remarkable performance of the electricity-triggered drug release profile. The drugs could be released with electrical stimulation, while there was almost no drug release without electrical stimulation. For AD treatment in vivo, this MN patch with electricity-triggered drug release performance could effectively deliver more drugs into the skin compared with other controls such as dexamethasone cream, which efficiently alleviate AD. In sum, this work not only developed a smart patch for improving AD treatment but also provided a promising approach of transdermal drug delivery on demand.

Graphene-based nanomaterials for cancer therapy and anti-infections.

Graphene-based nanomaterials (GBNMs) has been thoroughly investigated and extensively used in many biomedical fields, especially cancer therapy and bacteria-induced infectious diseases treatment, which have attracted more and more attentions due to the improved therapeutic efficacy and reduced reverse effect. GBNMs, as classic two-dimensional (2D) nanomaterials, have unique structure and excellent physicochemical properties, exhibiting tremendous potential in cancer therapy and bacteria-induced infectious diseases treatment. In this review, we first introduced the recent advances in development of GBNMs and GBNMs-based treatment strategies for cancer, including photothermal therapy (PTT), photodynamic therapy (PDT) and multiple combination therapies. Then, we surveyed the research progress of applications of GBNMs in anti-infection such as antimicrobial resistance, wound healing and removal of biofilm. The mechanism of GBNMs was also expounded. Finally, we concluded and discussed the advantages, challenges/limitations and perspective about the development of GBNMs and GBNMs-based therapies. Collectively, we think that GBNMs could be potential in clinic to promote the improvement of cancer therapy and infections treatment.