Examining the feasibility of assisted index case testing for HIV case-finding: a qualitative analysis of barriers and facilitators to implementation in Malawi.

BACKGROUND: Assisted index case testing (ICT), in which health care workers take an active role in referring at-risk contacts of people living with HIV for HIV testing services, has been widely recognized as an evidence-based intervention with high potential to increase status awareness in people living with HIV. While the available evidence from eastern and southern Africa suggests that assisted ICT can be an effective, efficient, cost-effective, acceptable, and low-risk strategy to implement in the region, it reveals that feasibility barriers to implementation exist. This study aims to inform the design of implementation strategies to mitigate these feasibility barriers by examining "assisting" health care workers' experiences of how barriers manifest throughout the assisted ICT process, as well as their perceptions of potential opportunities to facilitate feasibility. METHODS: In-depth interviews were conducted with 26 lay health care workers delivering assisted ICT in Malawian health facilities. Interviews explored health care workers' experiences counseling index clients and tracing these clients' contacts, aiming to inform development of a blended learning implementation package. Transcripts were inductively analyzed using Dedoose coding software to identify and describe key factors influencing feasibility of assisted ICT. Analysis included multiple rounds of coding and iteration with the data collection team. RESULTS: Participants reported a variety of barriers to feasibility of assisted index case testing implementation, including sensitivities around discussing ICT with clients, privacy concerns, limited time for assisted index case testing amid high workloads, poor quality contact information, and logistical obstacles to tracing. Participants also reported several health care worker characteristics that facilitate feasibility (knowledge, interpersonal skills, non-stigmatizing attitudes and behaviors, and a sense of purpose), as well as identified process improvements with the potential to mitigate barriers. CONCLUSIONS: Maximizing assisted ICT's potential to increase status awareness in people living with HIV requires equipping health care workers with effective training and support to address and overcome the many feasibility barriers that they face in implementation. Findings demonstrate the need for, as well as inform the development of, implementation strategies to mitigate barriers and promote facilitators to feasibility of assisted ICT. TRIAL REGISTRATION: NCT05343390. Date of registration: April 25, 2022.

PSAT1 mediated EMT of colorectal cancer cells by regulating Pl3K/AKT signaling pathway.

Background: The metastasis of colorectal cancer (CRC) is one of the significant barriers impeding its treated consequence and bring about high mortality, less surgical resection rate and poor prognosis of CRC patients. PSAT1 is an enzyme involved in serine biosynthesis. The studies showed that PSAT1 plays the part of a crucial character in the regulation of tumor metastasis. And Epithelial-Mesenchymal Transition (EMT) is a process of cell reprogramming in which epithelialcells obtain mesenchymal phenotypes. It is a crucial course in promoting cell metastasis and the progression of malignant tumors. The relationship between PSAT1 and EMT in colorectal cancer, as well as the underlying molecular mechanisms, remains enigmatic and warrants thorough exploration. These findings suggest that PSAT1 may serve as a promising therapeutic target for mitigating colorectal cancer metastasis and holds the potential to emerge as a valuable prognostic biomarker in forthcoming research endeavors. Materials and Methods: Utilizing TCGA dataset in conjunction with clinical CRC specimens, our initial focus was directed towards an in-depth examination of PSAT1 expression within CRC, specifically exploring its potential correlation with the adverse prognostic outcomes experienced by patients. Furthermore, we conducted a comprehensive investigation into the regulatory influence exerted by PSAT1 on CRC through the utilization of siRNA knockdown techniques. In the realm of in vitro experimentation, we meticulously evaluated the impact of PSAT1 on various facets of CRC progression, including cell migration, invasion, proliferation, and colony formation. In order to elucidate the intricate effects in question, we adopted a multifaceted methodology that encompassed a range of assays and analyses. These included wound healing assays, transwell assays, utilization of the Cell Counting Kit-8 (CCK-8) assay, and colony formation assays. By employing this diverse array of investigative techniques, we were able to achieve a comprehensive comprehension of the multifaceted role that PSAT1 plays in the pathogenesis of colorectal cancer. This multifarious analysis greatly contributed to our in-depth understanding of the complex mechanisms at play in colorectal cancer pathogenesis. Using WB and PCR experiments, we found that PSAT1 has a role in regulating EMT development in CRC.In terms of mechanism, we found that PSAT1 affected EMT by Regulating Pl3K/AKT Signaling Pathway. Results: Our investigation revealed a noteworthy down-regulation of PSAT1 expression in CRC specimens. Importantly, this down-regulation exhibited a significant positive correlation with the unfavorable prognosis of patients afflicted with CRC. Functionally, our study showcased that the siRNA-mediated knockdown of PSAT1 markedly enhanced various key aspects of CRC pathogenesis in an in vitro setting. Specifically, this included a substantial promotion of CRC cell migration, invasion, proliferation, and colony formation. Moreover, the silencing of PSAT1 also demonstrated a substantial promotion of the EMT process. Intriguingly, our research unveiled a hitherto unexplored mechanism underlying the regulatory role of PSAT1 in CRC and EMT. We have established, for the first time, that PSAT1 exerts its influence by modulating the activation of the PI3K/AKT Signaling Pathway. This mechanistic insight provides a valuable contribution to the understanding of the molecular underpinnings of CRC progression and EMT induction mediated by PSAT1. Conclusions: In unison, our research findings shed light on the previously uncharted and significant role of the PSAT1/PI3K/AKT axis in the initiation of the EMT process in CRC. Furthermore, our discoveries introduce a novel biomarker with potential implications for the clinical diagnosis and treatment of CRC.

Cu/Co Bimetallic Carbon Catalyst as a Highly Efficient Promoter for Reactive Dyes Degradation with PMS.

The synergistic effect between bimetallic catalysts has been confirmed as an effective method for activating persulfate (PMS). Therefore, we immobilized copper-cobalt on chitosan to prepare bimetallic carbon catalysts for PMS activation and degradation of reactive dyes. Experimental results demonstrate that the CuCo-CTs/PMS catalytic degradation system exhibits excellent degradation performance toward various types of reactive dyes (e.g., Ethyl violet, Chlortalidone, and Di chlorotriazine), with degradation rates reaching 90% within 30 min. CuCo-CTs exhibit high catalytic activity over a wide pH range of 3-11 at room temperature and under static conditions, degrading over 92% of RV5 within 60 min. ultraviolet-visible (UV-vis) spectroscopy and color changes in the dye solution confirm the effective degradation of RV5, with a degradation rate of 97.2% within 10 min. Additionally, CuCo-CTs demonstrate good stability and reusability, maintaining a degradation rate of 92.8% after eight cycles. Kinetic studies indicate that the degradation follows pseudo-first-order kinetics. Furthermore, based on the results of radical scavenging experiments, the catalytic degradation mechanism of the dye involves both radical and nonradical pathways, with 1O2 identified as the primary active species. This study provides insights and experimental evidence for the application of persulfate oxidation in the treatment of dyeing wastewater.

Accelerating PROTACs Discovery Through a Direct-to-Biology Platform Enabled by Modular Photoclick Chemistry.

Proteolysis targeting chimeras (PROTACs) have emerged as a promising strategy for drug discovery and exploring protein functions, offering a revolutionary therapeutic modality. Currently, the predominant approach to PROTACs discovery mainly relies on an empirical design-synthesis-evaluation process involving numerous cycles of labor-intensive synthesis-purification and bioassay data collection. Therefore, the development of innovative methods to expedite PROTAC synthesis and exploration of chemical space remains highly desired. Here, a direct-to-biology strategy is reported to streamline the synthesis of PROTAC libraries on plates, enabling the seamless transfer of reaction products to cell-based bioassays without the need for additional purification. By integrating amide coupling and light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) photoclick chemistry into a plate-based synthetic process, this strategy produces PROTAC libraries with high efficiency and structural diversity. Moreover, by employing this platform for PROTACs screening, we smoothly found potent PROTACs effectively inhibit triple-negative breast cancer (TNBC) cell growth and induce rapid, selective targeted degradation of cyclin-dependent kinase 9 (CDK9). The study introduces a versatile platform for assembling PROTACs on plates, followed by direct biological evaluation. This approach provides a promising opportunity for high-throughput synthesis of PROTAC libraries, thereby enhancing the efficiency of exploring chemical space and accelerating the discovery of PROTACs.

Does wearing a mask promote consumer uniqueness seeking?

As a motivational factor, uniqueness drives individuals to seek and choose unique goods or experiences. The act of wearing masks obscures individuals' facial features and influences their desire for uniqueness. This study aims to explore how wearing masks promotes individual uniqueness- seeking behavior. Three experiments were performed using various product categories (Starbucks coffee cups, sweatshirts, suitcases, and baseball caps) and sample types (college student and adult samples). Experiment results show that wearing masks obscures individuals' facial features and weakens their self- perceived uniqueness, thereby increasing their willingness to actively purchase unique products. This study is the first to examine the effect of wearing masks on individuals' choice of unique products. Practically, the results suggest that customized products can compensate for the lack of self-perceived uniqueness brought about by facial occlusion, thus providing valuable guidance for companies and retailers that offer customized services in formulating and designing marketing strategies.

Sodium-glucose co-transporter 1 promotes the bio-functions of perivascular preadipocytes mediated by Akt/mTOR/p70S6K signaling pathway.

The influence of SGLT-1 on perivascular preadipocytes (PVPACs) and vascular remodeling is not well understood. This study aimed to elucidate the role and mechanism of SGLT-1-mediated PVPACs bioactivity. PVPACs were cultured in vitro and applied ex vivo to the carotid arteries of mice using a lentivirus-based thermosensitive in situ gel (TISG). The groups were treated with Lv-SGLT1 (lentiviral vector, overexpression), Lv-siSGLT1 (RNA interference, knockdown), or specific signaling pathway inhibitors. Assays were conducted to assess changes in cell proliferation, apoptosis, glucose uptake, adipogenic differentiation, and vascular remodeling in the PVPACs. Protein expression was analyzed by western blotting, immunocytochemistry, and/or immunohistochemistry. The methyl thiazolyl tetrazolium (MTT) assay and Hoechst 33342 staining indicated that SGLT-1 overexpression significantly promoted PVPACs proliferation and inhibited apoptosis in vitro. Conversely, SGLT-1 knockdown exerted the opposite effect. Oil Red O staining revealed that SGLT-1 overexpression facilitated adipogenic differentiation, while its inhibition mitigated these effects. 3H-labeled glucose uptake experiments demonstrated that SGLT-1 overexpression enhanced glucose uptake by PVPACs, whereas RNA interference-mediated SGLT-1 inhibition had no significant effect on glucose uptake. Moreover, RT-qPCR, western blotting, and immunofluorescence analyses revealed that SGLT-1 overexpression upregulated FABP4 and VEGF-A levels and activated the Akt/mTOR/p70S6K signaling pathway, whereas SGLT-1 knockdown produced the opposite effects. In vivo studies corroborated these findings and indicated that SGLT-1 overexpression facilitated carotid artery remodeling. Our study demonstrates that SGLT-1 activation of the Akt/mTOR/p70S6K signaling pathway promotes PVPACs proliferation, adipogenesis, glucose uptake, glucolipid metabolism, and vascular remodeling.

Quantum phase synchronization via exciton-vibrational energy dissipation sustains long-lived coherence in photosynthetic antennas.

The lifetime of electronic coherences found in photosynthetic antennas is known to be too short to match the energy transfer time, rendering the coherent energy transfer mechanism inactive. Exciton-vibrational coherence time in excitonic dimers which consist of two chromophores coupled by excitation transfer interaction, can however be much longer. Uncovering the mechanism for sustained coherences in a noisy biological environment is challenging, requiring the use of simpler model systems as proxies. Here, via two-dimensional electronic spectroscopy experiments, we present compelling evidence for longer exciton-vibrational coherence time in the allophycocyanin trimer, containing excitonic dimers, compared to isolated pigments. This is attributed to the quantum phase synchronization of the resonant vibrational collective modes of the dimer, where the anti-symmetric modes, coupled to excitonic states with fast dephasing, are dissipated. The decoupled symmetric counterparts are subject to slower energy dissipation. The resonant modes have a predicted nearly 50% reduction in the vibrational amplitudes, and almost zero amplitude in the corresponding dynamical Stokes shift spectrum compared to the isolated pigments. Our findings provide insights into the mechanisms for protecting coherences against the noisy environment.

Evaluation of serum CA125, HE4 and CA724 and the risk of ovarian malignancy algorithm score in the diagnosis of high-grade serous ovarian cancer.

AIM: To develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC). METHODS: Patients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort. RESULTS: This study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups.Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort. CONCLUSION: The new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC.

Prediction of cross-border spread of the COVID-19 pandemic: A predictive model for imported cases outside China.

The COVID-19 pandemic has been present globally for more than three years, and cross-border transmission has played an important role in its spread. Currently, most predictions of COVID-19 spread are limited to a country (or a region), and models for cross-border transmission risk assessment remain lacking. Information on imported COVID-19 cases reported from March 2020 to June 2022 was collected from the National Health Commission of China, and COVID-19 epidemic data of the countries of origin of the imported cases were collected on data websites such as WHO and Our World in Data. It is proposed to establish a prediction model suitable for the prevention and control of overseas importation of COVID-19. Firstly, the SIR model was used to fit the epidemic infection status of the countries where the cases were exported, and most of the r2 values of the fitted curves obtained were above 0.75, which indicated that the SIR model could well fit different countries and the infection status of the region. After fitting the epidemic infection status data of overseas exporting countries, on this basis, a SIR-multiple linear regression overseas import risk prediction combination model was established, which can predict the risk of overseas case importation, and the established overseas import risk model overall P <0.05, the adjusted R2 = 0.7, indicating that the SIR-multivariate linear regression overseas import risk prediction combination model can obtain better prediction results. Our model effectively estimates the risk of imported cases of COVID-19 from abroad.

A Comprehensive Review on Reductive Recycling of Cathode Materials of Spent Lithium-Ion Batteries.

The prosperity of the lithium-ion battery market is inevitably accompanied by the depletion of corresponding resources and the accumulation of spent batteries in a dialectical manner. Spent lithium-ion batteries are harboring the characteristics of hazardous waste and high-value resources, so efficient recycling is of great significance. The cathode material is considered as an interesting target for repurposing. Despite some important reviews give commendable emphasis to recycling technologies, there is still a dearth of exploration of recycling mechanisms. This deficiency of awareness highlights the need for further research and development in this area. This review aims to systematically review and thoroughly discuss the reduction reaction mechanism of each method regarding different cathode materials. And systematically digest the selection of reducing agent and the effect of reduction reaction on material regeneration are systematically digested, as well as the impact of the reduction reaction on the regeneration of materials. This review emphasizes the importance of balancing efficiency, economic and environmental benefits in reuse technologies. Finally, the review proposes an outlook on the opportunities and challenges facing the reuse of key materials for next-generation spent batteries aimed at promoting the green and sustainable development of lithium-ion batteries, circular economy and ecological balance.

Gate-Tunable Quantum Acoustoelectric Transport in Graphene.

Transport probes the motion of quasi-particles in response to external excitations. Apart from the well-known electric and thermoelectric transport, acoustoelectric transport induced by traveling acoustic waves has rarely been explored. Here, by adopting hybrid nanodevices integrated with piezoelectric substrates, we establish a simple design of acoustoelectric transport with gate tunability. We fabricate dual-gated acoustoelectric devices based on hBN-encapsulated graphene on LiNbO3. Longitudinal and transverse acoustoelectric voltages are generated by launching a pulsed surface acoustic wave. The gate dependence of zero-field longitudinal acoustoelectric signal presents strikingly similar profiles to that of Hall resistivity, providing a valid approach for extracting carrier density without magnetic field. In magnetic fields, acoustoelectric quantum oscillations appear due to Landau quantization, which are more robust and pronounced than Shubnikov-de Haas oscillations. Our work demonstrates a feasible acoustoelectric setup with gate tunability, which can be extended to the broad scope of various van der Waals materials.

NLRX1: a key regulator in mitochondrial respiration and colorectal cancer progression.

Colorectal cancer (CRC) is a prevalent and aggressive malignancy with high mortality rates and significant risks to human well-being. Population-wide screening for tumor suppressor genes and oncogenes shows promise for reducing the incidence and fatality of CRC. Recent studies have suggested that NLRX1, an innate immunity suppressor, may play a role in regulating chronic inflammation and tumorigenesis. However, further investigation is needed to understand the specific role of NLRX1 in CRC. To evaluate the impact of NLRX1 on migration, invasion, and metastasis, two human colon cancer cell lines were studied in vitro. Additionally, a knockout mouse tumor-bearing model was used to validate the inhibitory effect of NLRX1 on tumor emergence and progression. The Seahorse XF96 technology was employed to assess mitochondrial function and glycolysis in colorectal cancer cells overexpressing NLRX1. Moreover, public databases were consulted to analyze gene and protein expression levels of NLRX1. Finally, the results were validated using a series of CRC patient samples. Our findings demonstrate that downregulation of NLRX1 enhances proliferation, colony formation, and tumor-forming capacity in HCT116 and LoVo cells. Conversely, overexpression of NLRX1 negatively impacts basal respiration and mitochondrial ATP-linked respiration in both cell lines, resulting in a notable decrease in maximal respiration during the standard mitochondrial stress test. Furthermore, analysis of data from the TCGA database reveals a significant reduction in NLRX1 expression in colon and rectal cancer tissues compared to normal tissues. This result was validated using clinical samples, where immunohistochemistry staining and western blotting demonstrated a notable reduction in NLRX1 protein levels in CRC compared to adjacent normal tissues. The decreased expression of NLRX1 may serve as a significant prognostic indicator and diagnostic biomarker for CRC patients.

A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/fl mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10afl/fl mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/fl mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10afl/fl molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Red/NIR-I-Fluorescence Carbon Dots Based on Rhein with Active Oxygen Scavenging and Colitis Targeting for UC Therapeutics.

Ulcerative colitis (UC) is a chronic inflammatory disease with uncontrolled inflammation and demage to the intestinal barrier. Rhein, a bioactive compound in traditional Chinese medicine, has anti-inflammatory and intestinal repair effect. However, their clinical application is limited by their hydrophobicity and poor bioavailability. L-arginine, as a complement to NO, has synergistic and attenuating effects. In this paper, red/NIR-I fluorescent carbon dots based on rhein and doped with L-arginine (RA-CDs), which are synthesized by a hydrothermal process without any organic solvents, are reported. RA-CDs preserve a portion of the functional group of the active precursor, increase rhein solubility, and emit red/NIR-I light for biological imaging. In vitro experiments show that RA-CDs scavenge excessive reactive oxygen species (ROS), protect cells from oxidative stress, and enable the fluorescence imaging of inflamed colons. In a DSS-induced UC mouse model, both delayed and prophylactic treatment with RA-CDs via intraperitoneal and tail vein injections alleviate UC severity by reducing intestinal inflammation and restoring the intestinal barrier. This study highlights a novel strategy for treating and imaging UC with poorly soluble small-molecule drugs.

High Level of Serum Complement C3 Expression is Associated with Postoperative Vasculopathy Progression in Moyamoya Disease.

Background: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD. Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression. Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables. Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late-Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.

The aldehyde dehydrogenase 2 rs671 variant enhances amyloid ß pathology.

In the ALDH2 rs671 variant, a guanine changes to an adenine, resulting in a dramatic decrease in the catalytic activity of the enzyme. Population-based data are contradictory about whether this variant increases the risk of Alzheimer's disease. In East Asian populations, the prevalence of the ALDH2 rs671 variant is 30-50%, making the National Human Brain Bank for Development and Function (the largest brain bank in East Asia) an important resource to explore the link between the ALDH2 rs671 polymorphism and Alzheimer's disease pathology. Here, using 469 postmortem brains, we find that while the ALDH2 rs671 variant is associated with increased plaque deposits and a higher Aß40/42 ratio, it is not an independent risk factor for Alzheimer's disease. Mechanistically, we show that lower ALDH2 activity leads to 4-HNE accumulation in the brain. The (R)-4-HNE enantiomer adducts to residue Lys53 of C99, favoring Aß40 generation in the Golgi apparatus. Decreased ALDH2 activity also lowers inflammatory factor secretion, as well as amyloid ß phagocytosis and spread in brains of patients with Alzheimer's disease. We thus define the relationship between the ALDH2 rs671 polymorphism and amyloid ß pathology, and find that ALDH2 rs671 is a key regulator of Aß40 or Aß42 generation.

Bioactive peptide relieves glucocorticoid-induced osteoporosis by giant macrocyclic encapsulation.

Bioactive peptides play a crucial role in the field of regenerative medicine and tissue engineering. However, their application in vivo and clinic is hindered by their poor stability, short half-life, and low retention rate. Herein, we propose a novel strategy for encapsulating bioactive peptides using giant macrocycles. Platelet-derived growth factor (PDGF) bioactive mimicking peptide Nap-FFGVRKKP (P) was selected as the representative of a bioactive peptide. Quaterphen[4]arene (4) exhibited extensive host-guest complexation with P, and the binding constant was (1.16 ± 0.10) × 107 M-1. In vitro cell experiments confirmed that P + 4 could promote the proliferation of BMSCs by 2.27 times. Even with the addition of the inhibitor dexamethasone (Dex), P + 4 was still able to save 76.94% of the cells in the control group. Compared to the Dex group, the bone mass of the mice with osteoporosis in the P + 4 group was significantly increased. The mean trabecular thickness (Tb.Th) increased by 17.03%, and the trabecular bone volume fraction (BV/TV) values increased by 40.55%. This supramolecular bioactive peptide delivery strategy provides a general approach for delivering bioactive peptides and opens up new opportunities for the development of peptide-based drugs.

Impact of HER2-low expression on the efficacy of endocrine therapy with or without CDK4/6 inhibitor in HR-positive/HER2-negative metastatic breast cancer: A prospective study.

BACKGROUND: CDK4/6 inhibitors in combination with traditional endocrine therapy (ET) have become the recommended first-line therapy for HR-positive/HER2-negative metastatic breast cancer (MBC). The aim of this prospective study was to evaluate the relationship between HER2-low expression and clinical outcomes in HR-positive/HER2-negative MBC patients receiving ET with or without CDK4/6 inhibitors. METHODS: Between April 2016 and November 2019, 233 women with HR-positive/HER2-negative MBC who received ET with or without CDK4/6 inhibitors were enrolled into the study. The primary endpoint was progression-free survival (PFS). Statistical analysis included descriptive statistics, Kaplan-Meier curves, and Cox proportional hazards models. RESULTS: HER2-low and HER2-zero subgroups in the CDK4/6 inhibitor plus ET cohort showed no significant difference in the median PFS (10.9 vs. 8.0 months; hazard ratio: 0.92; 95% confidence interval [CI]: 0.64-1. 30; p = 0.65), while HER2-low subgroup showed a significantly shorter median PFS compared to the HER2-zero subgroup in the ET alone cohort (5.6 vs. 17.0 months; hazard ratio: 2.82; 95% CI: 1.34-5.93; p = 0.0044). Moreover, the objective response rate was significantly lower in the HER2-low subgroup than the HER2-zero subgroup in the ET alone cohort (10.5% vs. 40.0%, p = 0.047). Lastly, no significant difference was observed in the overall survival between the HER2-low and HER2-zero subgroups in both cohorts. CONCLUSION: This study suggested that HER2-low expression may predict the efficacy of ET but not that of CDK4/6 inhibitor plus ET in HR-positive/HER2-negative MBC patients. The results of this study highlight the importance of integrating HER2 status in tailoring personalized treatment strategies for HR-positive MBC.

3D Point Cloud Object Detection Method Based on Multi-Scale Dynamic Sparse Voxelization.

Perception plays a crucial role in ensuring the safety and reliability of autonomous driving systems. However, the recognition and localization of small objects in complex scenarios still pose challenges. In this paper, we propose a point cloud object detection method based on dynamic sparse voxelization to enhance the detection performance of small objects. This method employs a specialized point cloud encoding network to learn and generate pseudo-images from point cloud features. The feature extraction part uses sliding windows and transformer-based methods. Furthermore, multi-scale feature fusion is performed to enhance the granularity of small object information. In this experiment, the term "small object" refers to objects such as cyclists and pedestrians, which have fewer pixels compared to vehicles with more pixels, as well as objects of poorer quality in terms of detection. The experimental results demonstrate that, compared to the PointPillars algorithm and other related algorithms on the KITTI public dataset, the proposed algorithm exhibits improved detection accuracy for cyclist and pedestrian target objects. In particular, there is notable improvement in the detection accuracy of objects in the moderate and hard quality categories, with an overall average increase in accuracy of about 5%.

Trauma plays an important role in acral melanoma: A retrospective study of 303 patients.

INTRODUCTION: Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. METHODS: A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. RESULTS: Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. CONCLUSION: This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.