Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.

Azulene-Containing Bis(squaraine) Dyes: Design, Synthesis and Aggregation Behaviors.

The relationship among chemical structure, physicochemical property and aggregation behavior of organic functional material is an important research topic. Here, we designed and synthesized three bis(squaraine) dyes BSQ1, BSQ2 and BSQ3 through the combination of two kinds of unsymmetrical azulenyl squaraine monomers. Their physicochemical properties were investigated in both molecular and aggregate states. Generally, BSQ1 displayed different assembly behaviors from BSQ2 and BSQ3. Upon fabrication into nanoparticles, BSQ1 tend to form J-aggregates while BSQ2 and BSQ3 tend to form H-aggregates in aqueous medium. When in the form of thin films, three bis(squaraine) dyes all adopted J-aggregation packing modes while only BSQ1 presented the most significant rearrangement of aggregate structures as well as the improvement in the carrier mobilities upon thermal annealing. Our research highlights the discrepancy of aggregation behaviors originating from the molecular structure and surrounding circumstances, providing guidance for the molecular design and functional applications of squaraines.

Preliminary field validity of ActiGraph-based energy expenditure estimation in wheelchair users with spinal cord injury.

STUDY DESIGN: Cross-sectional validation study. OBJECTIVES: To develop a raw acceleration signal-based random forest (RF) model for predicting total energy expenditure (TEE) in manual wheelchair users (MWUs) and evaluate the preliminary field validity of this new model, along with four existing models published in prior literature, using the Doubly Labeled Water (DLW) method. SETTING: General community and research institution in Pittsburgh, USA. METHODS: A total of 78 participants' data from two previous studies were used to develop the new RF model. A seven-day cross-sectional study was conducted to collect participants' free-living physical activity and TEE data, resting metabolic rate, demographics, and anthropometrics. Ten MWUs with spinal cord injury (SCI) completed the study, with seven participants having valid data for evaluating the preliminary field validity of the five models. RESULTS: The RF model achieved a mean absolute error (MAE) of 0.59 ± 0.60 kcal/min and a mean absolute percentage error (MAPE) of 23.6% ± 24.3% on the validation set. For preliminary field validation, the five assessed models yielded MAE from 136 kcal/day to 1141 kcal/day and MAPE from 6.1% to 50.2%. The model developed by Nightingale et al. in 2015 achieved the best performance (MAE: 136 ± 96 kcal/day, MAPE: 6.1% ± 4.7%), while the RF model achieved comparable performance (MAE: 167 ± 99 kcal/day, MAPE: 7.4% ± 5.1%). CONCLUSIONS: Two existing models and our newly developed RF model showed good preliminary field validity for assessing TEE in MWUs with SCI and the potential to detect lifestyle change in this population. Future large-scale field validation studies and model iteration are recommended.

A reciprocal relationship between parental maltreatment and child bullying perpetration in China.

This study aimed to examine the longitudinal reciprocal relationship between parental maltreatment and child bullying perpetration from middle childhood to early adolescence in China and the associated gender differences. Eight hundred ninety-one children completed a battery of questionnaires at four time points. A random-intercept cross-lagged model was established. The results indicated that at the between-person level, child bullying perpetration was positively associated with physical and psychological maltreatment. At the within-person level, there was a significant association between an increase in bullying perpetration and an increase in parental psychological and physical maltreatment across the four time points. Conversely, an increase in physical maltreatment led to an increase in child bullying perpetration from T1 to T2, while an increase in psychological maltreatment resulted in an increase in child bullying perpetration from T1 to T2 and T2 to T3. Furthermore, an increase in physical maltreatment increased boys' bullying perpetration but decreased that in girls from T2 to T3. These findings provide inspiration for future family education and anti-bullying interventions in schools.

A Membrane-Anchoring Self-Assembling Peptide Allows Bioorthogonal Coupling of Type-I AIEgens for Pyroptosis-Induced Cancer Therapy.

Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide-modified sugars-based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane-anchoring pure type-I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin-2 receptor (CCK2R) dual-targeting peptide named DBCO-pYCCK6, which can selectively and rapidly self-assemble on cancer cell membrane, and then bioorthogonal enrich type-I aggregation-induced emission luminogens (AIEgen) PSs (SAIE-N3) on the cell membrane. Upon light irradiation, the membrane-anchoring SAIE-N3 could effectively generate type-I reactive oxygen species (ROS) to induce gasdermin E (GSDME)-mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self-assembly peptide-mediated bioorthogonal reaction strategy to bridge the supramolecular self-assembly and AIE field through strain-promoted azide-alkyne cycloaddition (SPAAC) and elucidates that pure type-I membrane-anchoring PSs can be used for cancer therapy via GSDME-mediated pyroptosis.

π-π Interaction-Induced Organic Long-wavelength Room-Temperature Phosphorescence for In Vivo Atherosclerotic Plaque Imaging.

Room-temperature phosphorescent (RTP) materials have great potential for in vivo imaging because they can circumvent the autofluorescence of biological tissues. In this study, a class of organic-doped long-wavelength (≈600 nm) RTP materials with benzo[c][1,2,5] thiadiazole as a guest was constructed. Both host and guest molecules have simple structures and can be directly purchased commercially at a low cost. Owing to the long phosphorescence wavelength of the doping system, it exhibited good tissue penetration (10 mm). Notably, these RTP nanoparticles were successfully used to image atherosclerotic plaques, with a signal-to-background ratio (SBR) of 44.52. This study provides a new approach for constructing inexpensive red organic phosphorescent materials and a new method for imaging cardiovascular diseases using these materials.

Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

An Organophosphorescence Probe with Ultralong Lifetime and Intrinsic Tissue Selectivity for Specific Tumor Imaging and Guided Tumor Surgery.

Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. In addition, there have been few reports on organic phosphorescent materials that specifically distinguish tumors from normal tissues. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo-phosphorescent material with a lifetime of 0.94 s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood-rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room-temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments.

Semiconducting Polymers for Cancer Immunotherapy.

As a monumental breakthrough in cancer treatment, immunotherapy has attracted tremendous attention in recent years. However, one challenge faced by immunotherapy is the low response rate and the immune-related adverse events (irAEs). Therefore, it is important to explore new therapeutic strategies and platforms for boosting therapeutic benefits and decreasing the side effects of immunotherapy. In recent years, semiconducting polymer (SP), a category of organic materials with π-conjugated aromatic backbone, has been attracting considerable attention because of their outstanding characteristics such as excellent photophysical features, good biosafety, adjustable chemical flexibility, easy fabrication, and high stability. With these distinct advantages, SP is extensively explored for bioimaging and photo- or ultrasound-activated tumor therapy. Here, the recent advancements in SP-based nanomedicines are summarized for enhanced tumor immunotherapy. According to the photophysical properties of SPs, the cancer immunotherapies enabled by SPs with the photothermal, photodynamic, or sonodynamic functions are highlighted in detail, with a particular focus on the construction of combination immunotherapy and activatable nanoplatforms to maximize the benefits of cancer immunotherapy. Herein, new guidance and comprehensive insights are provided for the design of SPs with desired photophysical properties to realize maximized effectiveness of required biomedical applications.

X-ray Single Exposure Imaging and Image Processing of Objects with High Absorption Ratio.

The dynamic range of an X-ray digital imaging system is very important when detecting objects with a high absorption ratio. In this paper, a ray source filter is used to filter the low-energy ray components which have no penetrating power to the high absorptivity object to reduce the X-ray integral intensity. This enables the effective imaging of the high absorptivity objects and avoids the image saturation of low absorptivity objects, thus achieving single exposure imaging of high absorption ratio objects. However, this method will reduce the image contrast and weaken the image structure information. Therefore, this paper proposes a contrast enhancement method for X-ray images based on Retinex. Firstly, based on Retinex theory, the multi-scale residual decomposition network decomposes the image into an illumination component and a reflection component. Then, the contrast of the illumination component is enhanced through the U-Net model with the global-local attention mechanism, and the reflection component is enhanced in detail using the anisotropic diffused residual dense network. Finally, the enhanced illumination component and the reflected component are fused. The results show that the proposed method can effectively enhance the contrast in X-ray single exposure images of the high absorption ratio objects, and can fully display the structure information of images on devices with low dynamic range.

Synergistic mechanism of iron manganese supported biochar for arsenic remediation and enzyme activity in contaminated soil.

This study prepared and characterized bamboo-derived biochar loaded with different ratios of iron and manganese; evaluated its remediation performance in arsenic-contaminated soil by studying the changes in various environmental factors, arsenic speciation, and arsenic leaching amount in the soil after adding different materials; proposed the optimal ratio and mechanism of iron-manganese removal of arsenic; and explained the multivariate relationship between enzyme activity and soil environmental factors based on biological information. Treatment with Fe-Mn-modified biochar increased the organic matter, cation exchange capacity, and N, P, K, and other nutrient contents. During the remediation process, O-containing functional groups such as Mn-O/As and Fe-O/As were formed on the surface of the biochar, promoting the transformation of As from the mobile fraction to the residual fraction and reducing the phytotoxicity of As, and the remediation ability for As was superior to that of Fe-modified biochar. Mn is indispensable in the FeMn-BC synergistic remediation of As, as it can increase the adsorption sites and the number of functional groups for trace metals on the surface of biochar. In addition to electrostatic attraction, the synergistic mechanism of ferromanganese-modified biochar for arsenic mainly involves redox and complexation. Mn oxidizes As(Ⅲ) to more inert As(V). In this reaction process, Mn(Ⅳ) is reduced to Mn(Ⅲ) and Mn(II), promoting the formation of Fe(Ⅲ) and the conversion of As into Fe-As complexes, while As is fixed due to the formation of ternary surface complexes. Moreover, the effect of adding Fe-Mn-modified biochar on soil enzyme activity was correlated with changes in soil environmental factors; catalase was correlated with soil pH; neutral phosphatase was correlated with soil organic matter; urease was correlated with ammonia nitrogen, and sucrase activity was not significant. This study highlights the potential value of FM1:3-BC as a remediation agent in arsenic-contaminated neutral soils.

[Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer].

Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.

Amplification of Activated Near-Infrared Afterglow Luminescence by Introducing Twisted Molecular Geometry for Understanding Neutrophil-Involved Diseases.

Understanding the mechanism and progression of neutrophil-involved diseases (e.g., acute inflammation) is of great importance. However, current available analytical methods neither achieve the real-time monitoring nor provide dynamic information during the pathological processes. Herein, a peroxynitrite (ONOO-) and environmental pH dual-responsive afterglow luminescent nanoprobe is designed and synthesized. In the presence of ONOO- at physiological pH, the nanoprobes show activated near-infrared afterglow luminescence, whose intensity and lasting time can be highly enhanced by introducing the aggregation-induced emission (AIE) effect with a twisted molecular geometry into the system. In vivo studies using three diseased animal models demonstrate that the nanoprobes can sensitively reveal the development process of acute skin inflammation including infiltration of first arrived neutrophils and acidification initiating time, make a fast and accurate discrimination between allergy and inflammation, and rapidly screen the antitumor drugs capable of inducing immunogenic cell death. This work provides an alternative approach and advanced probes permitting precise disease monitoring in real time.

A Supramolecular Self-Assembling Nanoagent by Inducing Intracellular Aggregation of PSMA for Prostate Cancer Molecularly Targeted Theranostics.

Prostate cancer (PCa) with prostate-specific membrane antigen (PSMA)-specific high expression is well suited for molecularly targeted theranostics. PSMA expression correlates with the malignancy of PCa, and its dimeric form can promote tumor progression by exerting enzymatic activity to activate downstream signal transduction. However, almost no studies have shown that arresting the procancer signaling of the PSMA receptors themselves can cause tumor cell death. Meanwhile, supramolecular self-assembling peptides are widely used to design anticancer agents due to their unique and excellent properties. Here, a PSMA-targeting supramolecular self-assembling nanotheranostic agent, DBT-2FFGACUPA, which actively targets PSMA receptors on PCa cell membranes and induces them to enter the cell and form large aggregates, is developed. This process not only selectively images PSMA-positive tumor cells but also suppresses the downstream procancer signals of PSMA, causing tumor cell death. This work provides an alternative approach and an advanced agent for molecularly targeted theranostics options in PCa that can induce tumor cell death without relying on any reported anticancer drugs.

Expression and clinical significance of miR-204 in patients with hypertensive disorder complicating pregnancy.

OBJECTIVE: Hypertensive disorder complicating pregnancy (HDCP) is a unique and common obstetrical complication in pregnancy. The current study sought to investigate the diagnostic value of serum miR-204 in HDCP patients. METHODS: A total of 196 HDCP patients were enrolled, with 54 healthy pregnant women as controls. The expression levels of miR-204 and inflammatory factors in the serum were determined. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-204 in HDCP patients. Person coefficient was introduced to analyze the correlation between miR-204 and inflammatory indexes. Kaplan-Meier method was employed to analyze the effect of miR-204 expression on the incidence of adverse pregnancy outcomes. Logistic regression was adopted to assess the risk factors for adverse pregnancy outcomes. RESULTS: miR-204 expression was upregulated in the serum of HDCP patients. The serum miR-204 level > 1.432 could assist the diagnosis of HDCP. miR-204 level in the serum was positively correlated with TNF-α, IL-6, and hs-CRP concentrations in HDCP patients. The risk of adverse outcomes was higher in pregnant women with high miR-204 expression. High miR-204 expression was associated with an increased risk of adverse pregnancy outcomes after adjusting the family history of HDCP, systolic pressure, diastolic pressure, AST, ALT, LDH, 24-h urinary protein, TNF-α, IL-6, and hs-CRP. CONCLUSION: The high expression of miR-204 assists the diagnosis of HDCP and is an independent risk factor for adverse pregnancy outcomes in HDCP patients.

Toward Improving the Prediction of Functional Ambulation After Spinal Cord Injury Through the Inclusion of Limb Accelerations During Sleep and Personal Factors.

OBJECTIVE: To determine if functional measures of ambulation can be accurately classified using clinical measures; demographics; personal, psychosocial, and environmental factors; and limb accelerations (LAs) obtained during sleep among individuals with chronic, motor incomplete spinal cord injury (SCI) in an effort to guide future, longitudinal predictions models. DESIGN: Cross-sectional, 1-5 days of data collection. SETTING: Community-based data collection. PARTICIPANTS: Adults with chronic (>1 year), motor incomplete SCI (N=27). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ambulatory ability based on the 10-m walk test (10MWT) or 6-minute walk test (6MWT) categorized as nonambulatory, household ambulator (0.01-0.44 m/s, 1-204 m), or community ambulator (>0.44 m/s, >204 m). A random forest model classified ambulatory ability using input features including clinical measures of strength, sensation, and spasticity; demographics; personal, psychosocial, and environmental factors including pain, environmental factors, health, social support, self-efficacy, resilience, and sleep quality; and LAs measured during sleep. Machine learning methods were used explicitly to avoid overfitting and minimize the possibility of biased results. RESULTS: The combination of LA, clinical, and demographic features resulted in the highest classification accuracies for both functional ambulation outcomes (10MWT=70.4%, 6MWT=81.5%). Adding LAs, personal, psychosocial, and environmental factors, or both increased the accuracy of classification compared with the clinical/demographic features alone. Clinical measures of strength and sensation (especially knee flexion strength), LA measures of movement smoothness, and presence of pain and comorbidities were among the most important features selected for the models. CONCLUSIONS: The addition of LA and personal, psychosocial, and environmental features increased functional ambulation classification accuracy in a population with incomplete SCI for whom improved prognosis for mobility outcomes is needed. These findings provide support for future longitudinal studies that use LA; personal, psychosocial, and environmental factors; and advanced analyses to improve clinical prediction rules for functional mobility outcomes.

Predicting physical activity intensity using raw accelerometer signals in manual wheelchair users with spinal cord injury.

STUDY DESIGN: Cross-sectional validation study. OBJECTIVES: The performance of previously published physical activity (PA) intensity cutoff thresholds based on proprietary ActiGraph counts for manual wheelchair users (MWUs) with spinal cord injury (SCI) was initially evaluated using an out-of-sample dataset of 60 individuals with SCI. Two types of PA intensity classification models based on raw accelerometer signals were developed and evaluated. SETTING: Research institutions in Pittsburgh PA, Birmingham AL, and Bronx NY. METHODS: Data were collected from 60 MWUs with SCI who followed a structured activity protocol while wearing an ActiGraph activity monitor on their dominant wrist and portable metabolic cart which measured criterion PA intensity. Data was used to assess published models as well as develop and assess custom models using recall, specificity, precision, as well as normalized Mathew's correlation coefficient (nMCC). RESULTS: All the models performed well for predicting sedentary vs non-sedentary activity, yielding an nMCC of 0.87-0.90. However, all models demonstrated inadequate performance for predicting moderate to vigorous PA (MVPA) with an nMCC of 0.76-0.82. CONCLUSIONS: The mean absolute deviation (MAD) cutoff threshold yielded the best performance for predicting sedentary vs non-sedentary PA and may be used for tracking daily sedentary activity. None of the models displayed strong performance for MVPA vs non-MVPA. Future studies should investigate combining physiological measures with accelerometry to yield better prediction accuracies for MVPA.

The role of vaginal microecology in the cervical cancer.

AIM: To explore the role of vaginal microecology in cervical cancer, so as to increase the understanding of cervical cancer and lay a foundation for future large-sample clinical trials. METHODS: We reviewed and summarized the literature comprehensively, and discussed the relationship between vaginal microecology and HPV infection, CIN progression and cervical cancer, as well as the potential molecular mechanism and the prospects of probiotics and prebiotics in future cancer treatments. RESULTS: With the popularization of high-throughput sequencing technology and the development of bioinformatics analysis technology, many evidences show that the increase in the diversity of the bacterial community in the vaginal microecological environment and the decrease in the number of Lactobacilli are associated with the continuous infection of HPV and the further development of CIN, cervical cancer-related. CONCLUSIONS: Vaginal microecological imbalance has an important impact on the occurrence and development of cervical cancer. However, the pathogenesis is not completely clear, and more high-level basic research and longitudinal clinical studies are needed to verify.

Limb accelerations during sleep are related to measures of strength, sensation, and spasticity among individuals with spinal cord injury.

BACKGROUND: To evaluate the relationship between measures of neuromuscular impairment and limb accelerations (LA) collected during sleep among individuals with chronic spinal cord injury (SCI) to provide evidence of construct and concurrent validity for LA as a clinically meaningful measure. METHODS: The strength (lower extremity motor score), sensation (summed lower limb light touch scores), and spasticity (categorized lower limb Modified Ashworth Scale) were measured from 40 adults with chronic (≥ 1 year) SCI. Demographics, pain, sleep quality, and other covariate or confounding factors were measured using self-report questionnaires. Each participant then wore ActiGraph GT9X Link accelerometers on their ankles and wrist continuously for 1-5 days to measure LA from movements during sleep. Regression models with built-in feature selection were used to determine the most relevant LA features and the association to each measure of impairment. RESULTS: LA features were related to measures of impairment with models explaining 69% and 73% of the variance (R²) in strength and sensation, respectively, and correctly classifying 81.6% (F1-score = 0.814) of the participants into spasticity categories. The most commonly selected LA features included measures of power and frequency (frequency domain), movement direction (correlation between axes), consistency between movements (relation to recent movements), and wavelet energy (signal characteristics). Rolling speed (change in angle of inclination) and movement smoothness (median crossings) were uniquely associated with strength. When LA features were included, an increase of 72% and 222% of the variance was explained for strength and sensation scores, respectively, and there was a 34% increase in spasticity classification accuracy compared to models containing only covariate features such as demographics, sleep quality, and pain. CONCLUSION: LA features have shown evidence of having construct and concurrent validity, thus demonstrating that LA are a clinically-relevant measure related to lower limb strength, sensation, and spasticity after SCI. LA may be useful as a more detailed measure of impairment for applications such as clinical prediction models for ambulation.