Intermittent blood flow restriction with low-load resistance training for older adults with knee osteoarthritis: a randomized, controlled, non-inferiority trial protocol.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.

Stretchable MXene/Carbon Nanotube Bilayer Strain Sensors with Tunable Sensitivity and Working Ranges.

Stretchable strain sensors have gained increasing popularity as wearable devices to convert mechanical deformation of the human body into electrical signals. Two-dimensional transition metal carbides (Ti3C2Tx MXene) are promising candidates to achieve excellent sensitivity. However, MXene films have been limited in operating strain ranges due to rapid crack propagation during stretching. In this regard, this study reports MXene/carbon nanotube bilayer films with tunable sensitivity and working ranges. The device is fabricated using a scalable process involving spray deposition of well-dispersed nanomaterial inks. The bilayer sensor's high sensitivity is attributed to the cracks that form in the MXene film, while the compliant carbon nanotube layer extends the working range by maintaining conductive pathways. Moreover, the response of the sensor is easily controlled by tuning the MXene loading, achieving a gauge factor of 9039 within 15% strain at 1.92 mg/cm2 and a gauge factor of 1443 within 108% strain at 0.55 mg/cm2. These tailored properties can precisely match the operation requirements during the wearable application, providing accurate monitoring of various body movements and physiological activities. Additionally, a smart glove with multiple integrated strain sensors is demonstrated as a human-machine interface for the real-time recognition of hand gestures based on a machine-learning algorithm. The design strategy presented here provides a convenient avenue to modulate strain sensors for targeted applications.

Development of an indirect competitive ELISA based on the common epitope of fish parvalbumin for its detection.

A common epitope (AGSFDHKKFFKACGLSGKST) of parvalbumin from 16 fish species was excavated using bioinformatics tools combined with the characterization of fish parvalbumin binding profile of anti-single epitope antibody in this study. A competitive enzyme-linked immunosorbent assay (ELISA) based on the common epitope was established with a limit of detection of 10.15 ng/mL and a limit of quantification of 49.29 ng/mL. The developed ELISA exhibited a narrow range (71% to 107%) of related cross-reactivity of 15 fish parvalbumin. Besides, the recovery, the coefficient of variations for the intra-assay and the inter-assay were 84.3% to 108.2%, 7.4% to 13.9% and 8.5% to 15.6%. Our findings provide a novel idea for the development of a broad detection method for fish allergens and a practical tool for the detection of parvalbumin of economic fish species in food samples.

Prediction of Follicular Thyroid Neoplasm and Malignancy of Follicular Thyroid Neoplasm Using Multiparametric MRI.

The study aims to evaluate multiparametric magnetic resonance imaging (MRI) for differentiating Follicular thyroid neoplasm (FTN) from non-FTN and malignant FTN (MFTN) from benign FTN (BFTN). We retrospectively analyzed 702 postoperatively confirmed thyroid nodules, and divided them into training (n = 482) and validation (n = 220) cohorts. The 133 FTNs were further split into BFTN (n = 116) and MFTN (n = 17) groups. Employing univariate and multivariate logistic regression, we identified independent predictors of FTN and MFTN, and subsequently develop a nomogram for FTN and a risk score system (RSS) for MFTN prediction. We assessed performance of nomogram through its discrimination, calibration, and clinical utility. The diagnostic performance of the RSS for MFTN was further compared with the performance of the Thyroid Imaging Reporting and Data System (TIRADS). The nomogram, integrating independent predictors, demonstrated robust discrimination and calibration in differentiating FTN from non-FTN in both training cohort (AUC = 0.947, Hosmer-Lemeshow P = 0.698) and validation cohort (AUC = 0.927, Hosmer-Lemeshow P = 0.088). Key risk factors for differentiating MFTN from BFTN included tumor size, restricted diffusion, and cystic degeneration. The AUC of the RSS for MFTN prediction was 0.902 (95% CI 0.798-0.971), outperforming five TIRADS with a sensitivity of 73.3%, specificity of 95.1%, accuracy of 92.4%, and positive and negative predictive values of 68.8% and 96.1%, respectively, at the optimal cutoff. MRI-based models demonstrate excellent diagnostic performance for preoperative predicting of FTN and MFTN, potentially guiding clinicians in optimizing therapeutic decision-making.

Clostridioides difficile-mucus interactions encompass shifts in gene expression, metabolism, and biofilm formation.

In a healthy colon, the stratified mucus layer serves as a crucial innate immune barrier to protect the epithelium from microbes. Mucins are complex glycoproteins that serve as a nutrient source for resident microflora and can be exploited by pathogens. We aimed to understand how the intestinal pathogen, Clostridioides difficile, independently uses or manipulates mucus to its benefit, without contributions from members of the microbiota. Using a 2-D primary human intestinal epithelial cell model to generate physiologic mucus, we assessed C. difficile-mucus interactions through growth assays, RNA-Seq, biophysical characterization of mucus, and contextualized metabolic modeling. We found that host-derived mucus promotes C. difficile growth both in vitro and in an infection model. RNA-Seq revealed significant upregulation of genes related to central metabolism in response to mucus, including genes involved in sugar uptake, the Wood-Ljungdahl pathway, and the glycine cleavage system. In addition, we identified differential expression of genes related to sensing and transcriptional control. Analysis of mutants with deletions in highly upregulated genes reflected the complexity of C. difficile-mucus interactions, with potential interplay between sensing and growth. Mucus also stimulated biofilm formation in vitro, which may in turn alter the viscoelastic properties of mucus. Context-specific metabolic modeling confirmed differential metabolism and the predicted importance of enzymes related to serine and glycine catabolism with mucus. Subsequent growth experiments supported these findings, indicating mucus is an important source of serine. Our results better define responses of C. difficile to human gastrointestinal mucus and highlight flexibility in metabolism that may influence pathogenesis. IMPORTANCE: Clostridioides difficile results in upward of 250,000 infections and 12,000 deaths annually in the United States. Community-acquired infections continue to rise, and recurrent disease is common, emphasizing a vital need to understand C. difficile pathogenesis. C. difficile undoubtedly interacts with colonic mucus, but the extent to which the pathogen can independently respond to and take advantage of this niche has not been explored extensively. Moreover, the metabolic complexity of C. difficile remains poorly understood but likely impacts its capacity to grow and persist in the host. Here, we demonstrate that C. difficile uses native colonic mucus for growth, indicating C. difficile possesses mechanisms to exploit the mucosal niche. Furthermore, mucus induces metabolic shifts and biofilm formation in C. difficile, which has potential ramifications for intestinal colonization. Overall, our work is crucial to better understand the dynamics of C. difficile-mucus interactions in the context of the human gut.

An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

BACKGROUND: Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. METHODS: Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. RESULTS: The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. CONCLUSION: In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

Dual-Stimuli Regulation of DNAzyme Cleavage Reaction by Coordination-Driven Nanoprobes for Cancer Cell Imaging.

Endowing current artificial chemical reactions (ACRs) with high specificity and intricate activation capabilities is crucial for expanding their applications in accurate bioimaging within living cells. However, most of the reported ACR-based evaluations relied on either single biomarker stimuli or dual activators without obvious biological relevance, still limiting their accuracy and fidelity. Herein, taking the metal-ion-dependent DNAzyme cleavage reaction as a model ACR, two regulators, glutathione (GSH) and telomerase (TE) activated DNAzyme cleavage reactions, were exploited for precise discrimination of cancerous cells from normal cells. DNA probe was self-assembled into the ZIF-90 nanoparticle framework to construct coordination-driven nanoprobes. This approach enhances the stability and specificity of tumor imaging by utilizing biomarkers associated with rapid tumor proliferation and those commonly overexpressed in tumors. In conclusion, the research not only paves the way for new perspectives in cell biology and pathology studies but also lays a solid foundation for the advancement of biomedical imaging and disease diagnostic technologies.

Influence of vegetation on heavy metal Cr release process from bottom sediment under unidirectional flows and regular waves.

As human activities become more intensive, a substantial number of heavy metals are discharged into estuarine or wetland environments. Due to the poor degradability, heavy metals are prone to adsorption and deposition on suspended particles in bottom sediments. Subsequently, under the influence of disturbances, there is a potential for their re-release, causing secondary pollution. To investigate the release process of the heavy metal Cr from sediment, laboratory experiments were conducted under both unidirectional flow and regular wave conditions. At the initial stage, the temporal trends of particulate (CrP) and dissolved (CrD) Chromium concentrations were both characterized by initial increments followed by stabilization and continuous escalation. Vertically, the stable concentrations of CrP and CrD increased with the presence of vegetation and the enhancement of hydrodynamics. The Elovich equation, pseudo-second-order kinetic equation, Double constant equation (Freundlich model), and parabolic diffusion equation were employed to predict the release process of CrD from bottom sediment. The Elovich equation proved most suitable for describing the release process of CrD, with an R2 exceeding 0.9. In order to assess the influence of vegetation on the Cr release process, the Stem-Reynolds were introduced to modify the Elovich equation. The final maximum error was 12 % (excluding the initial stage), which was much lower than that using the original Elovich equation (maximum error of 32 %). The study findings provide practical support for estuarine and wetland managers to formulate effective heavy metal management measures, which contribute to the conservation and sustainable management of aquatic ecosystems.

PURPL Promotes M2 Macrophage Polarization in Lung Cancer by Regulating RBM4/xCT Signaling.

Lung cancer is the most common malignancy worldwide. Long non-coding RNA (lncRNA) p53 upregulated regulator of P53 levels (PURPL) is abnormally in various cancers. However, the reports on its roles in lung cancer are limited. The purpose of present study is to investigate the potentials of lncRNA PURPL in lung cancer. PURPL and mRNA expression was determined using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). The location of PURPL was detected using RNA fluorescence in situ hybridization (FISH) assay. Protein expression was detected using western blot. Cellular functions were determined using flow cytometry. The interaction between PURPL and RNA-binding motif 4 (RBM4) was confirmed using RNA immunoprecipitation (RIP) assay. PURPL was overexpressed in lung cancer cells and patients. Overexpressed PURPL promoted M2 macrophage polarization and suppressed ferroptosis. Additionally, PURPL maintained the mRNA stability of cystine glutamate reverse transporter (xCT) via regulating RBM4. xCT knockdown antagonized the effects of overexpressed PURPL and inhibited M2 macrophage polarization via inducing macrophage ferroptosis. PURPL/RBM4/xCT axis promoted M2 macrophage polarization in lung cancer. Therefore, PURPL may be a potential target of lung cancer.

A robust aluminum-octacarboxylate framework with scu topology for selective capture of sulfur dioxide.

The high structural diversity and porosity of metal-organic frameworks (MOFs) promote their applications in selective gas adsorption. The development of robust MOFs that are stable against corrosive SO2 remains a daunting challenge. Here, we report a highly robust aluminum-based MOF (HIAM-330) built on a 4-connected Al3(OH)2(COO)4 cluster and 8-connected octacarboxylate ligand with a (4,8)-connected scu topology. It exhibits a fully reversible SO2 uptake of 12.1 mmol g-1 at 298 K and 1 bar. It is capable of selective capture of SO2 over other gases (CO2, CH4, and N2) with high adsorption selectivities of 60, 330, and 3537 for equimolar mixtures of SO2/CO2, SO2/CH4, and SO2/N2, respectively, at 298 K and 1 bar. Breakthrough measurements verified the capability of HIAM-330 for selective capture of SO2 (2500 ppm) over CO2 or N2. High-resolution synchrotron X-ray powder diffraction of SO2 loaded HIAM-330 revealed the binding domains of adsorbed SO2 molecules and host-guest interactions.

Orientation transitions and chiral assemblies of para-terphenyl molecules on Cd(0001).

The interplay between orientation transition and chiral self-assemblies of para-terphenyl (P3P) molecules on the Cd(0001) surface has been investigated using low temperature scanning tunneling microscopy and density functional theory calculations. Three distinct molecular orientations have been discerned from the self-assembled thin films of P3P. At the low coverage, flat-lying molecules appear in the homochiral domains with the incommensurate registry to the substrate. With the coverage increasing, the incoming molecules are incorporated into the first layer with edge-on orientation and form the self-assembled zigzag chains. The alternative arrangement of zigzag chains with opposite chirality leads to the formation of a c(4 × 2) superstructure, in which the tilted molecules exhibit orientational frustration and fuzzy noises. The analysis of the tunneling spectra reveals that the electronic structure of P3P layers is contingent upon the hybridization between the electronic states of P3P molecules and the Cd(0001) surface. These results provide important insights into the interplay between orientational transition and chiral assembly of P3P molecules on metal substrates.

Discovery of a novel DYRK1A inhibitor with neuroprotective activity by virtual screening and in vitro biological evaluation.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is implicated in accumulation of amyloid ß-protein (Aß) and phosphorylation of Tau proteins, and thus represents an important therapeutic target for neurodegenerative diseases. Though many DYRK1A inhibitors have been discovered, there is still no marketed drug targeting DYRK1A. This is partly due to the lack of effective and safe chemotypes. Therefore, it is still necessary to identify new classes of DYRK1A inhibitors. By performing virtual screening with the workflow mainly composed of pharmacophore modeling and molecular docking as well as the following DYRK1A inhibition assay, we identified compound L9, ((Z)-1-(((5-phenyl-1H-pyrazol-4-yl)methylene)-amino)-1H-tetrazol-5-amine), as a moderately active DYRK1A inhibitor (IC50: 1.67 µM). This compound was structurally different from the known DYRK1A inhibitors, showed a unique binding mode to DYRK1A. Furthermore, compound L9 showed neuroprotective activity against okadaic acid (OA)-induced injury in the human neuroblastoma cell line SH-SY5Y by regulating the expression of Aß and phosphorylation of Tau protein. This compound was neither toxic to the SH-SY5Y cells nor to the human normal liver cell line HL-7702 (IC50: >100 µM). In conclusion, we have identified a novel DYRK1A inhibitor with neuroprotective activity through virtual screening and in vitro biological evaluation, which holds the promise for further study.

Exposure to ambient air pollutants during circadian syndrome and subsequent cardiovascular disease and its subtypes and death: A trajectory analysis of the UK Biobank.

BACKGROUND: The association between exposure to air pollutants and cardiovascular disease (CVD) trajectory in individuals with circadian syndrome remains inconclusive. METHODS: The individual exposure levels of air pollutants, including particulate matter (PM) with aerodynamic diameter ≤ 2.5 µm (PM2.5), PM with aerodynamic diameter ≤ 10 µm (PM10), PM2.5 absorbance, PM with aerodynamic diameter between 2.5 µm and 10 µm, nitrogen dioxide (NO2), nitrogen oxides (NOx), and air pollution score (overall air pollutants exposure), were estimated for 48,850 participants with circadian syndrome from the UK Biobank. Multistate regression models were employed to estimate associations between exposure to air pollutants and trajectories from circadian syndrome to CVD/CVD subtypes (including coronary heart disease [CHD], atrial fibrillation [AF], heart failure [HF], and stroke) and death. Mediation roles of CVD/CVD subtypes in the associations between air pollutants and death were evaluated. RESULTS: After a mean follow-up time over 12 years, 12,570 cases of CVD occurred, including 8192 CHD, 1693 AF, 1085 HF, and 1600 stroke cases. In multistate model, per-interquartile range increment in PM2.5 (hazard ratio: 1.08; 95 % confidence interval: 1.06, 1.10), PM10 (1.04; 1.01, 1.06), PM2.5 absorbance (1.04; 1.02, 1.06), NO2 (1.07; 1.03, 1.11), NOx (1.08; 1.04, 1.12), or air pollution score (1.06; 1.03, 1.08) was associated with trajectory from circadian syndrome to CVD. Significant associations between the above-mentioned air pollutants and trajectories from circadian syndrome and CVD to death were observed. CVD, particularly CHD, significantly mediated the associations of PM2.5, NO2, NOx, and air pollution score with death. CONCLUSIONS: Long-term exposure to air pollutants during circadian syndrome was associated with subsequent CVD and death. CHD emerged as the most prominent CVD subtype in CVD progression driven by exposure to air pollutants during circadian syndrome. Our study highlights the importance of controlling air pollutants exposure and preventing CHD in people with circadian syndrome.

Associations of Plasma Metabolites With Risks of Incident Stroke and Its Subtypes in Chinese Adults.

BACKGROUND: Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. METHODS AND RESULTS: We performed a nested case-control study within the Dongfeng-Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow-up period of 6.1±2.3 years. Fifty-five metabolites in fasting plasma were measured by ultra-high-performance liquid chromatography-mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 [1.08-1.34] and 1.22 [1.09-1.36], respectively; both Benjamini-Hochberg-adjusted P <0.05). When examining stroke subtypes, asymmetrical/symmetrical dimethylarginine was nominally associated with both IS and HS (odds ratios [95% CIs]: 1.16 [1.03-1.31] and 1.39 [1.07-1.81], respectively), while glutamate was associated with only IS (odds ratios [95% CI]: 1.26 [1.11-1.43]). The associations of glutamate with IS risk were significantly stronger among participants with hypertension and diabetes than among those without these diseases (both P for interaction <0.05). CONCLUSIONS: This study validated the positive associations of asymmetrical/symmetrical dimethylarginine and glutamate with stroke risk, mainly that of IS, in a Chinese population, and revealed a novel unanimous association of with both IS and HS. Our findings provided potential intervention targets for stroke prevention.

Demonstration of charge-hold-vent (CHV) and no-vent-fill (NVF) in a simulated propellent storage tank during tank-to-tank cryogen transfer in microgravity.

The space exploration from a low earth orbit to a high earth orbit, then to Moon, Mars, and possibly asteroids and moons of other planets is one of the biggest challenges for scientists and engineers for the new millennium. The enabling of in-space cryogenic rocket engines and the Lower-Earth-Orbit (LEO) cryogenic fuel depots for these future manned and robotic space exploration missions begins with the technology development of advanced cryogenic thermal-fluid management systems for the propellant transfer line and storage tank system. One of the key thermal-fluid management operations is the chilldown and filling of the propellant storage tank in space. As a result, highly energy efficient, breakthrough concepts for quenching heat transfer to conserve and minimize the cryogen consumption during chilldown have become the focus of engineering research and development, especially for the deep-space mission to Mars. In this paper, we introduce such thermal transport concepts and demonstrate their feasibilities in space for cryogenic propellant storage tank chilldown and filling in a simulated space microgravity condition on board an aircraft flying a parabolic trajectory. In order to maximize the storage tank chilldown thermal efficiency for the least amount of required cryogen consumption, the breakthrough quenching heat transfer concepts developed include the combination of charge-hold-vent (CHV) and no-vent-hold (NVF). The completed flight experiments successfully demonstrated the feasibility of the concepts and discovered that spray cooling combined with hold and vent is more efficient than the pure spray cooling for storage tank chilldown in microgravity. In microgravity, the data shows that the CHV thermal efficiency can reach 39.5%. The CHV efficiency in microgravity is 6.9% lower than that in terrestrial gravity. We also found that pulsing the spray can increase CHV efficiency by 6.1% in microgravity.

Combinations of Energy-based Devices plus isotretinoin for management of acne and acne scars: A systematic review.

BACKGROUND AND OBJECTIVE: A 6-month interval between systemic isotretinoin (ISO) and the initiation of energy-based interventions has been recommended, due to concerns about keloid formation and delayed wound healing. While this postponement goes against the current trend of early intervention for acne scarring. This systematic review evaluates the efficacy, safety, and patient satisfaction of combinations of ISO with energy-based devices (EBD). STUDY DESIGN/METHODS AND MATERIALS: PubMed, Embase, Web of Science, Cochrane Library, and Cochrane Central Register of Controlled Trials were comprehensively searched up to April 2023 according to PRISMA guidelines. Two independent reviewers screened the titles and abstracts to select articles. The quality of the literature was assessed for each study design. RESULTS: A total of 16 studies addressing the efficacy and safety of energy-based modalities combined with ISO were identified, including six randomized controlled trials (RCTs), two case series, seven cohort studies, and one case report. ISO combinations with intense pulsed light (IPL), fractional ablative CO2 laser, pulsed dye laser (PDL), non-ablative fractional laser (NAFL) and fractional microneedle radiofrequency (FMRF) have been tested for improving acne severity, acne scarring and erythema. CONCLUSION: The current evidence does not justify delaying the use of EBDs for patients who have recently undergone or are currently receiving ISO treatment. Evidence-based treatments such as PDL, NAFL, and FMRF etc. are suggested relatively safe and effective in treating acne and acne scarring.

Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles.

Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (ED-sHDL) or chemically conjugated (CD-sHDL) DM1. We found that CD-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than ED-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving CD-sHDL, leading to a better efficacy and immune memory of CD-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 (CD-Lipo) showed lower immunotoxicity than those with entrapped drug (ED-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.