Neural signatures of default mode network subsystems in first-episode, drug-naive patients with major depressive disorder after 6-week thought induction psychotherapy treatment.

Evidence indicates that the default mode network (DMN) plays a crucial role in the neuropathology of major depressive disorder (MDD). However, the neural signatures of DMN subsystems in MDD after low resistance Thought Induction Psychotherapy (TIP) remain incompletely understood. We collected functional magnetic resonance imaging data from 20 first-episode, drug-naive MDD and 20 healthy controls (HCs). The DMN was segmented into three subsystems and seed-based functional connectivity (FC) was computed. After 6-week treatment, the significantly reduced FCs with the medial temporal lobe memory subsystem in MDD at baseline were enhanced and were comparable to that in HCs. Changed Hamilton Depression Rating Scale scores were significantly related with changed FC between the posterior cingulate cortex (PCC) and the right precuneus (PCUN). Further, changed serotonin 5-hydroxytryptamine levels were significantly correlated with changed FCs between the PCC and the left PCUN, between the posterior inferior parietal lobule and the left inferior temporal gyrus, and between the retrosplenial cortex and the right inferior frontal gyrus, opercular part. Finally, the support vector machine obtained an accuracy of 67.5% to distinguish between MDD at baseline and HCs. These findings may deepen our understanding of the neural basis of the effects of TIP on DMN subsystems in MDD.

Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC.

Individuals' continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both social competition and hierarchy. However, the molecular regulatory mechanisms underlying the neural ensemble in the mPFC remains unclear. Here, we demonstrate that in excitatory neurons of prelimbic cortex (PL), lncRNA Sera remodels the utilization of Pkm Exon9 and Exon10, resulting in a decrease in the Pkm1/2 ratio in highly competitive mice. By employing a tet-on/off system, we disrupt or rebuild the normal Pkm1/2 ratio by controlling the expression of Pkm2 in PL excitatory neurons. We find that long-term Pkm2 modulation induces timely competition alteration and hysteretic rank change, through phosphorylating the Ser845 site of GluA1. Together, this study uncovers a crucial role of lncRNA Sera/Pkm2 pathway in the transition of social competition to rank by remodeling neural ensemble in mPFC.

Optimizing Outcomes in Distal Tibial Deformity Correction: The Role of Supramalleolar Osteotomy with Computer-assisted Hexapod External Fixator.

OBJECTIVE: Distal tibial deformities can significantly impact patients if left uncorrected, often leading to pain, alterations in gait, and the eventual development of post-traumatic arthritis. The criteria for surgical correction in these patients continues to be a subject of debate, while supramalleolar osteotomy (SMO) is an effective method for correcting distal tibial deformities. The purpose of this study was to evaluate and compare the clinical results of SMO using internal fixation or using computer-assisted hexapod external fixator in the treatment of distal tibial deformity. METHODS: A retrospective study was conducted on 290 patients who underwent SMO between June 2015 and January 2023. Forty-four patients met the inclusion and exclusion criteria. Among the participants, 19 underwent SMO combined with a computer-assisted hexapod external fixator, while 25 received SMO with plate and screw internal fixation. The tibial anterior surface (TAS) angle, tibial lateral surface (TLS) angle, the tibiotalar (TT) angle and the talocrural (TC) angle were assessed on weight-bearing X-ray films. Functional assessments were performed according to the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: The study followed patients for an average duration of 31.7 ± 15.3 months, with a range from 12 to 67 months. Successful bone union was achieved in all cases. For patients treated with the computer-assisted hexapod external fixator, significant improvements were observed: the mean deviation in sagittal plane deformity parameters decreased from 14.3 ± 10.4 degrees preoperatively to 2.8 ± 3.8 degrees postoperatively (p < 0.05). Similarly, coronal plane deformity parameters showed a reduction from 25.9 ± 22.5 degrees preoperatively to 5.9 ± 11.0 degrees postoperatively (p < 0.05). The AOFAS ankle-hindfoot score improved markedly from 66.0 ± 14.9 to 86.1 ± 11.7 points (p < 0.05). For patients undergoing internal fixation, the absolute difference in coronal plane parameters improved from 15.4 ± 12.6 degrees preoperatively to 3.7 ± 3.4 degrees postoperatively (p < 0.05). A significant enhancement in AOFAS ankle-hindfoot score was also noted, increasing from 68.3 ± 14.3 points to 79.4 ± 13.5 points (p < 0.05). There were no significant differences in gender, side, follow-up time, postoperative deviation of deformity, pre- or postoperative AOFAS between the two groups. CONCLUSION: In conclusion, comprehensive preoperative planning of SMO combined with either internal fixation or a hexapod external fixator for treating distal tibial deformities can achieve satisfactory outcomes. The utilization of a computer-assisted hexapod external fixator facilitates a gradual and precise correction process, which proved to be an effective and relatively safe method.

AICyte-alone capabilities as an independent screener for triaging cervical cytology using a 50% negative cutoff value.

BACKGROUND: AICyte has previously demonstrated a potential role in cervical cytology screening for reducing the workload by using a 50% negative cutoff value. The aim of the current study is to evaluate this hypothesis. METHODS: The authors used the Ruiqian WSI-2400 (with the registered trademark AICyte) to evaluate a collection of 163,848 original cervical cytology cases from 2018 to 2023 that were collected from four different hospital systems in China. A breakdown of cases included 46,060 from Shenzhen, 67,472 from Zhengzhou, 25,667 from Shijiazhuang, and 24,649 from Jinan. These collected cases were evaluated using the AICyte system, and the data collected were statistically compared with the original interpretative results. RESULTS: In 98.80% of all artificial intelligence cases that were designated as not needing further review, the corresponding original diagnosis was also determined to be negative. For any cases that were designated atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion or higher, the sensitivity and negative predictive value were 90.77% and 98.80%, respectively. The sensitivity and negative predictive value were greater in cases designated as low-grade squamous intraepithelial lesion or higher at 98.92% and 99.94%, respectively. Of the 49 low-grade squamous intraepithelial lesion or higher that were designed by AICyte as not needing further review, the cytohistologic correlation revealed eight cases of cervical intraepithelial neoplasia 1 and 18 negative cases; and the remaining cases were without histologic follow-up. In practice, AICyte used at a 50% negative cutoff value could reduce the anticipated workload if a protocol were implemented to label cases that qualified within the negative cutoff value as not needing further review, thereby finalizing the case as negative for intraepithelial lesions and malignancy. CONCLUSIONS: For pathologic practices that do not have cytotechnologists or in which the workflow is sought to be optimized, the artificial intelligence system AICyte alone to be an independent screening tool by using a 50% negative cutoff value, which is a potential assistive method for cervical cancer screening.

Gradual Transverse Transport of Naturally Tibialized Fibula Using Hexapod Frames to Treat Neglected Type V Tibial Segmental Defects.

OBJECTIVE: Although several reconstructive methods have been developed to manage large segmental tibial bone defects including bone transport (distraction osteogenesis), contralateral fibular graft, allograft, tibiofibular synostosis, Masquelet technique, and 3D printed scaffold, neglected large tibial defects in adults remain challenging problems. This study describes gradual transverse transport of naturally tibialized fibula using hexapod frames in management of adult patients with neglected large tibial defects. METHODS: We retrospectively reviewed four cases of transverse transport of naturally tibialized fibula from November 2018 to February 2022. We measured the length of the tibial defect and the transported fibular segment, the mid-diaphyseal diameter and cortical thickness of the affected fibula, contralateral fibula, and tibia. The parameters measured both preoperatively and postoperatively were leg length discrepancy, hip-knee-ankle angle, medial proximal tibial angle, posterior proximal tibial angle, lateral distal tibial angle, range of motion of the knee and ankle joints, and Lower Extremity Functional Scores (LEFS). Patients' satisfaction rates using Likert scale were also recorded. RESULTS: Among four female patients, three suffered from tibial osteomyelitis, and one was due to congenital pseudarthrosis of the tibia. The average follow-up time was 2.7 ± 1.4 years. The average length of tibial defect was 14.0 ± 0.8 cm. The average preoperative shortening of the affected leg was 9.0 ± 2.5 cm, which changed to 0.6 ± 0.8 cm postoperatively. The median length of the transported fibular segment was 15.2 cm. Two patients had varus deformity, two had recurvatum, and one had procurvatum preoperatively. Postoperative radiological measurement showed all deformities corrected and no ankle valgus deformity developed during follow-up. All patients achieved union and can fully weight bear on the affected extremity. The average fixator time was 12.9 ± 2.9 months. The average preoperative and postoperative LEFS, respectively, were 53.5 ± 5.0, 70.5 ± 1.3, with a significant difference (p = 0.003). Three patients reported very satisfied with the outcome, and one patient reported satisfied. Three patients had pin tract infections, and one patient had skin necrosis which healed after additional surgery. One patient had surgical release of the hamstring tendons due to flexion contracture of the knee. Two patients had 15° of reduction in ankle range of motion. One patient had transient common peroneal nerve palsy which spontaneously recovered within 6 weeks. CONCLUSION: The transverse transport of naturally tibialized fibula was both a safe and effective method to treat the long-standing type V tibial segmental defect.

Evidence for Intermittent Theta Burst Transcranial Magnetic Stimulation for Dysphagia after Stroke: A Systematic Review and Meta-analysis.

Dysphagia is the most common serious complication after stroke, with an incidence of about 37-78%, which seriously affects the independence of patients in daily life and clinical recovery. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulation technique, is an emerging option for post-stroke dysphagia. Theta burst stimulation (TBS) is a new mode of transcranial magnetic stimulation that simulates the frequency of pulses released in the hippocampus.Intermittent theta burst stimulation (iTBS) has been shown to increase cortical excitability and improve swallowing function in patients. Our study sought to summarize existing clinical randomized controlled trials to provide evidence-based medical evidence for the clinical use of iTBS. A computer search was conducted on 4 Chinese (Chinese Biomedical Literature Database, VIP Information Resource System, CNKI, and Wanfang Medical Science) and 4 English (including Cochrane Library, Embase, PubMed, Web of Science) databases to retrieve all randomized controlled trials in Chinese and English that explored the effects of Intermittent Theta Burst Stimulation for post-stroke dysphagia. The retrieval years are from database construction to 23 November 2023. The primary outcome measure was a change in Penetration/Aspiration Scale (PAS), Standardized Swallowing Assessment (SSA) and Functional Oral Intake Scale (FOIS), Secondary outcomes included Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), water-swallowing test (WST) etc. A meta-analysis by Standardized Mean Difference (SMD) and 95% confidence interval (CI) was performed with RevMan 5.3. we appraise risk of bias(RoB) of each study with the Cochrane RoB tool. Detailed instructions for using the Cochrane RoB tool are provided in the Cochrane Handbook for Systematic Reviews of Interventions (The Cochrane Handbook). Nine studies were obtained from eight databases after screening by inclusion and exclusion criteria, 567 patients from 9 studies were included in the meta-analysis, and one study was included in the qualitative analysis due to different control groups. Two of the nine studies had an unclear risk of bias, and four studies were at low risk. The results showed that iTBS significantly improved SSA, PAS, FOIS, and PAS scores in stroke patients compared to the control group(P < 0.05), and promoted swallowing function recovery. Our systematic review provides the first evidence of the efficacy of iTBS in improving dysphagia in stroke patients. However, the number of available studies limits the persuasiveness of the evidence and further validation by additional randomized controlled trials is needed.

Association between fibrinogen levels and stroke-associated pneumonia in acute ischemic stroke patients.

PURPOSE: Prior research had indicated a relationship between fibrinogen and stroke-associated pneumonia (SAP), yet the nature of this relationship had not been thoroughly investigated. Therefore, this study was designed to elucidate the prognostic value of fibrinogen levels in forecasting the occurrence of SAP among patients with acute ischemic stroke (AIS). PATIENTS AND METHODS: In this retrospective cross-sectional analysis, we included 1092 patients who had experienced AIS and were admitted to our facility within 72 h of the onset of their symptoms. Based on the SAP diagnostic criteria, patients were classified into two groups: SAP and non-SAP. The correlation between serum fibrinogen concentration and SAP was examined using univariate analysis. Curve fitting and multivariable logistic regression model were utilized for statistical evaluation. RESULTS: Out of the ischemic stroke patients included in the study, SAP was identified in 112 (10.26%) patients. A direct correlation was observed between fibrinogen levels and the incidence of SAP. An increase in fibrinogen levels corresponded with a heightened incidence of SAP. Multivariable logistic regression revealed a significant positive association between fibrinogen levels and SAP incidence (OR = 1.53, 95% confidence interval [CI]: 1.18, 1.99)). CONCLUSION: A linear relationship between serum fibrinogen levels and the incidence of SAP in ischemic stroke patients was shown. The serum fibrinogen levels were positively and linearly correlated to SAP risk.

Analysis of radiologic parameters and clinical outcomes in supramalleolar osteotomy for varus ankle osteoarthritis: A novel method for evaluating ankle alignment.

BACKGROUND: Solely relying on the tibial ankle surface (TAS) angle for determining the mechanical ankle axis might be insufficient. We introduce a novel method to determine the distance from the center of the talus to the tibial axis (TTD). This study aimed to investigate the association between clinical outcomes and radiological changes before and after supramalleolar osteotomy (SMO), including TAS angle, talar tilt (TT) angle, tibiotalar surface (TTS) angle and TTD. METHODS: Seventy patients who received SMO were enrolled. Radiological changes were measured using weight-bearing anteroposterior imaging. The percentage of talar center displacement (TTDP) was calculated as the difference between postoperative and preoperative TTD, divided by talar width (TW). Clinical assessments were performed using the American Orthopedic Foot and Ankle Society ankle-hindfoot (AOFAS) scale. Differences in the aforementioned indicators before and after the operation were analyzed. We defined ΔAOFAS, ΔTAS, ΔTT and ΔTTS as the difference between postoperative and preoperative values. RESULTS: ΔTTS correlated with ΔAOFAS (r = 0.40, p = 0.008), as did TTDP (r = 0.32, p = 0.035). No correlation was observed between ΔAOFAS and ΔTAS. In the comparison between groups, patients with a TTDP greater than 26.19 exhibited a significantly greater ΔAOFAS. The high intraclass correlation coefficient indicated good reliability of the novel method. CONCLUSION: Solely relying on the TAS angle for tibial correction was insufficient. We found TTD as a novel method to evaluate mechanical ankle joint axis. TTDP and ΔTTS both positively correlated with ΔAOFAS, indicating the usefulness of these radiologic parameters.

Performance of P16INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for HPV-positive women aged 50 and above.

Background: Few articles have focused on the cytological misinterpretation of high-grade squamous intraepithelial lesion (HSIL). Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HSIL on Papanicolaou-stained cytology slides, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16 cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology. Objective: To evaluate the role of P16 cytology in differentiating cytology HSIL from benign atrophy in women aged 50 years and above. Methods: Included in this analysis were women in a cervical cancer screening project conducted in central China who tested positive for high-risk human papillomavirus (hr-HPV) and returned back for triage with complete data of primary HPV testing, liquid-based cytology (LBC) analysis, P16 immuno-stained cytology interpretation, and pathology diagnosis. The included patients were grouped by age: ≥50 (1,127 cases) and <50 years (1,430 cases). The accuracy of LBC and P16 cytology in the detection of pathology ≥HSIL was compared between the two groups, and the role of P16 immuno-stain in differentiating benign cervical lesions from cytology ≥HSIL was further analyzed. Results: One hundred sixty-seven women (14.8%; 167/1,127) in the ≥50 group and 255 (17.8%, 255/1,430) in the <50 group were pathologically diagnosed as HSIL (Path-HSIL). LBC [≥Atypical Squamous Cell Of Undetermined Significance (ASCUS)] and P16 cytology (positive) respectively detected 63.9% (163/255) and 90.2% (230/255) of the Path-≥HSIL cases in the <50 group and 74.3% (124/167) and 93.4% (124/167) of the Path-≥HSIL cases in the ≥50 group. LBC matched with pathology in 105 (41.2%) of the 255 Path-≥HSIL cases in the <50 group and 93 (55.7%) of the 167 Path-≥HSIL cases in the ≥50 group. There were five in the <50 group and 14 in the ≥50 group that were Path-≤LSIL cases, which were interpreted by LBC as HSIL, but negative in P16 cytology. Conclusion: P16 cytology facilitates differentiation of Path-≤LSIL from LBC-≥HSIL for women 50 years of age and above. It can be used in the lower-resource areas, where qualified cytologists are insufficient, as the secondary screening test for women aged ≥50 to avoid unnecessary biopsies and misinterpretation of LBC primary or secondary screening.

CLCuMuV subverts the processing of hydroxyproline-rich systemin to suppress tobacco defenses against insect vectors.

The interactions of insect vector-virus-plant have important ecological and evolutionary implications. The constant struggle of plants against viruses and insect vectors has driven the evolution of multiple defense strategies in the host as well as counter-defense strategies in the viruses and insect vectors. Cotton leaf curl Multan virus (CLCuMuV) is a major causal agent of cotton leaf curl disease in Asia and is exclusively transmitted by the whitefly Bemisia tabaci. Here, we report that plants infected with CLCuMuV and its betasatellite, cotton leaf curl Multan betasatellite (CLCuMuB) enhance the performance of B. tabaci vector, and ßC1 encoded by CLCuMuB plays an important role in begomovirus-whitefly-tobacco tripartite interactions. We showed that CLCuMuB ßC1 suppresses the jasmonic acid signaling pathway by interacting with the subtilisin-like protease 1.7 (NtSBT1.7) protein, thereby enhancing whitefly performance on tobacco plants. Further studies revealed that in the wild type plants, NtSBT1.7 could process tobacco preprohydroxyproline-rich systemin B (NtpreproHypSysB). After CLCuMuB infection, CLCuMuB ßC1 could interfere with the processing of NtpreproHypSysB by NtSBT1.7, thereby impairing plant defenses against whitefly. These results contribute to our understanding of the tripartite interactions among virus, plant, and whitefly, thus offering ecological insights into the spread of vector insect populations and the prevalence of viral diseases.

DNA-Mediated Magnetic-Dimer Assembly for Fault-Free Ultra-High-Field Magnetic Resonance Imaging of Tumors.

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.

Structural Defect-Enabled Magnetic Neutrality Nanoprobes for Ultra-High-Field Magnetic Resonance Imaging of Isolated Tumor Cells in Vivo.

The identification of metastasis "seeds," isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological-level insights. Recent advancements in ultra-high-field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization-induced strong T2-decaying effects under UHF conditions, which compromises T1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect-enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T2-decaying effect while concurrently enhancing UHF T1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r2/r1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16 mm. These high-performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF-MRI for diagnostic purposes and fostering comprehensive metastasis research.

Ni-based catalysts supported on Hbeta zeolite for the hydrocracking of waste polyolefins.

Polyolefin plastics are the most popular polymer materials worldwide, and the catalytic degradation of post-consumer polyolefins has attracted increased attention as a viable process. In this study, two types of Ni-based catalysts supported on Hbeta zeolite, Ni-Hbeta and NiS2-Hbeta, have been successfully synthesized for the hydrocracking of waste polyolefin. The experimental results indicated that the synergistic effect between Ni or NiS2 and the acidic sites of Hbeta zeolites can significantly enhance the tandem cracking and hydrogenation of polyolefin plastics, which suppresses the formation of gas products and coke. Ni-Hbeta employed as a catalyst can effectively degrade HDPE into high value liquid and gas products with high yield of 94% under 523 K and 3 MPa H2, while also exhibiting excellent cycle stability. In particular, Ni-Hbeta shows better catalytic performance than NiS2-Hbeta during the hydrocracking of HDPE at a relatively low temperature of 523 K. Furthermore, Ni-Hbeta catalyst also exhibits a remarkable capability for efficient depolymerization of unsorted post-consumer polyolefin plastics (HDPE, LDPE, PP) containing various additives and pollutants. These findings underscore the application potential of employing noble metal-free and recyclable catalysts for hydrocracking plastic waste, thereby facilitating the realization of a circular economy for plastics.

[Study on mechanism of inhibiting proliferation of head and neck cancer cells by citral, active ingredient of lemon essential oil].

To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer cells SCC15 and CAL33, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay(MTT) was utilized to identify the active component inhibiting the proliferation of head and neck cancer cells, namely citral. The IC_(50) of citral inhibiting the proliferation of head and neck cancer cells and normal cells were also determined. In addition, a 5-ethynyl-2'-deoxyuridine(EdU) staining assay was used to detect the effect of citral on the proliferation rate of head and neck cancer cells, and a colony formation assay was used to detect the effect of citral on tumor sphere formation of head and neck cancer cells in vitro. The cell cycle arrest and apoptosis induction of head and neck cancer cells by citral were evaluated by flow cytometry, and Western blot was used to detect the effect of citral on the expression levels of cell cycle-and apoptosis-related proteins in head and neck cancer cells. The findings indicated that citral could effectively inhibit the proliferation and growth of head and neck cancer cells, with anti-tumor activity, and its half inhibitory concentrations for CAL33 and SCC15 were 54.78 and 25.23 µg·mL~(-1), respectively. Furthermore, citral arrested cell cycle at G_2/M phase by down-regulating cell cycle-related proteins such as S-phase kinase associated protein 2(SKP2), C-MYC, cyclin dependent kinase 1(CDK1), and cyclin B. Moreover, citral increased the cysteinyl aspartate-specific proteinase-3(caspase-3), cysteinyl aspartate-specific proteinase-9(caspase-9), and cleaved poly ADP-ribose polymerase(PARP). It up-regulated the level of autophagy-related proteins including microtubule associated protein 1 light chain 3B(LC3B), sequestosome 1(P62/SQSTM1), autophagy effector protein Beclin1(Beclin1), and lysosome-associate membrane protein 1(LAMP1), suggesting that citral could effectively trigger cell apoptosis and cell autophagy in head and neck cancer cells. Furthermore, the dual-tagged plasmid system mCherry-GFP-LC3 was used, and it was found that citral impeded the fusion of autophagosomes and lysosomes, leading to autophagic flux blockage. Collectively, our findings reveal that the main active anti-proliferation component of lemon essential oil is citral, and this component has a significant inhibitory effect on head and neck cancer cells. Its underlying molecular mechanism is that citral induces apoptosis and autophagy by cell cycle arrest and ultimately inhibits cell proliferation.

[Effect of Shoutai Pills on expression of key glycolytic proteins and apoptosis related factors at maternal fetal interface in mouse model of threatened abortion with syndrome of kidney deficiency].

This study aims to explore the mechanism of Shoutai Pills in treating threatened abortion. According to the random number table method, ICR female mice were randomized into a normal group, a model group, a dydrogesterone group, and a Shoutai Pills group, with 15 mice in each group. Mice were administrated with normal saline(normal and model groups) or the suspension of Shoutai Pills or dydrogesterone by gavage at 9:00 am every day. At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days. ICR female and male mice were caged in a ratio of 2∶1 during the pre-estrous or estrous period. From the first day of pregnancy, drug administration was continued for 5 consecutive days. On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion. On day 6 of pregnancy, 10 female ICR mice were randomly selected from each group, and the uterus was collected for observation of the pathological changes of trophoblasts at the maternal-fetal interface by hematoxylin-eosin(HE) staining. The protein levels of key enzymes of glycolysis, hexokinase 2(HK2), enolase 1(ENO1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A(LDHA), were determined by Western blot and immunofluorescence. The expression of apoptosis-related proteins including B cell lymphoma-2(Bcl-2), Bcl-2-associated protein X(Bax), and cysteinyl aspartate-specific proteinase-3(caspase-3) was determined by Western blot and real-time PCR. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling was employed to examine apoptosis. The embryo loss rate of the remaining five female mice was calculated by trypan blue staining method on day 14 of pregnancy. On day 14 of pregnancy, the embryo loss rate of the normal group was 5.00%, which was lower than that(27.78%) in the model group(P<0.05). Dydrogesterone and Shoutai Pills groups showed reduced embryo loss rates(10.26% and 7.50%, respectively) compared with the model group. On day 6 of pregnancy, compared with the normal group, the model group showed down-regulated expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and up-regulated expression of Bax and caspase-3(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills up-regulated the expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and down-regulated the expression of Bax and caspase-3(P<0.05). Compared with that in the normal group, the apoptosis rate in the model group increased(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P<0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.

Ligand-Induced Atomically Segregation-Tunable Alloy Nanoprobes for Enhanced Magnetic Resonance Imaging.

Bimetallic iron-noble metal alloy nanoparticles have emerged as promising contrast agents for magnetic resonance imaging (MRI) due to their biocompatibility and facile control over the element distribution. However, the inherent surface energy discrepancy between iron and noble metal often leads to Fe atom segregation within the nanoparticle, resulting in limited iron-water molecule interactions and, consequently, diminished relaxometric performance. In this study, we present the development of a class of ligand-induced atomically segregation-tunable alloy nanoprobes (STAN) composed of bimetallic iron-gold nanoparticles. By manipulating the oxidation state of Fe on the particle surface through varying molar ratios of oleic acid and oleylamine ligands, we successfully achieve surface Fe enrichment. Under the application of a 9 T MRI system, the optimized STAN formulation, characterized by a surface Fe content of 60.1 at %, exhibits an impressive r1 value of 2.28 mM-1·s-1, along with a low r2/r1 ratio of 6.2. This exceptional performance allows for the clear visualization of hepatic tumors as small as 0.7 mm in diameter in vivo, highlighting the immense potential of STAN as a next-generation contrast agent for highly sensitive MR imaging.

Mismatch repair deficiency and abnormal p53 expression has significant predictive value for progesterone resistance and endometrial tumorigenesis in patients with endometrial atypical hyperplasia receiving fertility-preserving treatment.

OBJECTIVE: This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment. METHODS: This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status. RESULTS: Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively). CONCLUSIONS: EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.

Feasibility and applicability of self-sampling based online cervical cancer screening: findings from the China online cervical cancer screening trial.

OBJECTIVE: This study aims to evaluate the feasibility and applicability of an online cervical cancer screening program using a website as the public platform and self-collected HPV testing as the primary screening method. METHODS: A website (mcareu.com) was developed to facilitate the online cervical cancer screening program by Peking University Shenzhen Hospital (PUSH). Women in Shenzhen could register for participation on the website by providing essential demographic data. Sampling kits and specimens were delivered through regular logistics. Eligible women collected vaginal samples by themselves using the provided kits and in referring of the graphic guidance. The specimens were tested for HPV at PUSH or a reference lab, and the results were accessible on the website through participants' personal accounts. Participants who tested positive for high-risk HPV were scheduled for colposcopy and biopsies. The demographic and social background data of the eligible participants were analyzed to evaluate the feasibility and applicability of the online screening approach. RESULTS: A total of 1712 applicants registered for participation, with 99.9% (1710/1712) completing registration with full data. The analysis included 1560 applicants aged 30-59, with an average age of 41.1 (± 7.6) years. Among them, 83.3% (1299/1560) provided self-collected samples for testing. Age-group analysis revealed an overall sample provision rate (SPR) exceeded 80% in all age groups. A significant difference in SPR was observed only between the 30-34 and 45-49 age groups (p < 0.05), while no significant differences were found among other age groups. 99.7% of the samples were tested qualified, and there was no significant difference in sampling failure rate among age groups. Analysis of demographic and social elements showed no significant impact on the rates of sample provision among groups in most of the social elements but the medical insurance and the monthly family-incomes. CONCLUSION: The findings demonstrate that online cervical cancer screening is reliable for self-registration, self-sampling, and self-ordering for specimen transportation. It is suitable for women of all ages needing to be screened, irrespective of social elements, and effectively facilitates screening for women with limited access to medical resources. Therefore, online screening holds promise as an effective approach to increase screening coverage.