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Background Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing TKI resistance may involve targeting the renewal and repopulation of stem-like cells. To investigate the underlying mechanisms, we conducted RNA Microarray and m6A Epi-Transcriptomic Microarray analyses, followed by assessment of transcription factors. Additionally, we specifically designed a tag to detect the polypeptide circRNA-AA, and its expression was confirmed through m6A regulations. Results We initially identified unique molecular signatures present in cancer stem cells that contributed to poor therapeutic responses. Activation of the alternative Wnt pathway was found to sustain the renewal and resistant status of these cells. Through bioinformatics analysis and array studies, we observed a significant decrease in the expression of circFBXW7 in Osimertinib-resistant cell lines. Notably, the abnormal expression pattern of circFBXW7 determined the cellular response to Osimertinib. Functional investigations revealed that circFBXW7 inhibits the renewal of cancer stem cells and resensitizes both resistant LUAD cells and stem cells to Osimertinib. In terms of the underlying mechanism, we discovered that circFBXW7 can be translated into short polypeptides known as circFBXW7-185AA. These polypeptides interact with β-catenin in an m6A-dependent manner. This interaction leads to reduced stability of β-catenin by inducing subsequent ubiquitination, thereby suppressing the activation of canonical Wnt signaling. Additionally, we predicted that the m6A reader, YTHDF3, shares common binding sites with hsa-Let-7d-5p. Enforced expression of Let-7d post-transcriptionally decreases the levels of YTHDF3. The repression of Let-7d by Wnt signaling releases the stimulation of m6A modification by YTHDF3, promoting the translation of circFBXW7-185AA. This creates a positive feedback loop contributing to the cascade of cancer initiation and promotion. Conclusions Our bench study, in vivo experiments, and clinical validation have unequivocally shown that circFBXW7 effectively inhibits the abilities of LUAD stem cells and reverses resistance to TKIs by modulating Wnt pathway functions through the action of circFBXW7-185AA on β-catenin ubiquitination and inhibition. The regulatory role of circRNA in Osimertinib treatment has been rarely reported, and our findings reveal that this process operates under the influence of m6A modification. These results highlight the tremendous potential of this approach in enhancing therapeutic strategies and overcoming resistance to multiple TKI treatments.

The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here, we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons), whose firing rates display grooming-related modulation. Our study uncovers a new role of the ventral striatum’s IC in regulating motor output and has important implications for the neural control of grooming. Despite their discovery in the 19th century, the islands of Calleja, clusters of densely packed granule cells in the ventral striatum, remain enigmatic. This study reveals that islands of Calleja neurons are critical for grooming control in mice.

The ventral striatum is a reward center implicated in the pathophysiology of depression. It contains islands of Calleja, clusters of dopamine D3 receptor-expressing granule cells, predominantly in the olfactory tubercle (OT). These OT D3 neurons regulate self-grooming, a repetitive behavior manifested in affective disorders. Here we show that chronic restraint stress (CRS) induces robust depression-like behaviors in mice and decreases excitability of OT D3 neurons. Ablation or inhibition of these neurons leads to depression-like behaviors, whereas their activation ameliorates CRS-induced depression-like behaviors. Moreover, activation of OT D3 neurons has a rewarding effect, which diminishes when grooming is blocked. Finally, we propose a model that explains how OT D3 neurons may influence dopamine release via synaptic connections with OT spiny projection neurons (SPNs) that project to midbrain dopamine neurons. Our study reveals a crucial role of OT D3 neurons in bidirectionally mediating depression-like behaviors, suggesting a potential therapeutic target. Ventral striatal Islands of Calleja neurons, known to regulate grooming in mice, are reported to bidirectionally mediate depression-like behaviors. Here, authors link grooming, dopamine signaling and affective behaviors via ventral striatal circuits.

CO2, an abundant and renewable C1 source, presents significant potential for applications in organic synthesis. Hydrazones, recognized for their distinctive properties, exhibit high versatility in synthetic chemistry, facilitating numerous chemical transformations. Given their crucial roles in organic synthesis, the combination of CO2 with hydrazones has garnered increasing research interest. This review provides a comprehensive summary of recent progress in reactions involving CO2 and hydrazones or their derivatives. These include the coupling of amines and N-tosylhydrazones with CO2, the umpolung-mediated carboxylation of hydrazones/N-tosylhydrazones with CO2, the cyclization of hydrazones with CO2, and lactamization reactions incorporating N-tosylhydrazones and CO2. These transformations utilize the diverse reactivity of hydrazones and their derivatives to capture and convert CO2, generating valuable organic compounds with both academic and practical relevance. Additionally, the review examines the mechanisms underlying these reactions, offering critical insights for advancing research in this area.

Background The interference screw is the most popular device that fixes the graft for anterior cruciate ligament reconstruction, reducing the incidence of windshield effect and bungee effect. For the screw, either metallic, “bioresorbable,” or polyetheretherketone (PEEK) material is available. PEEK is popular and extensively used due to its stability, biocompatibility, radiolucency, and elastic modulus. Rare relevant complications were reported, but here, we report two cases of extra-articular migrations of PEEK interference screw from the tibial tunnel after anterior cruciate reconstruction. Case report An 18-year-old boy and a 56-year-old woman underwent anterior cruciate ligament reconstruction using a PEEK interference screw to fix the graft in the tibial tunnel. They suffered from screw extrusion from the tibial tunnel after 40 days and six months, respectively, with an incision rupture or palpable subcutaneous mass. They underwent a second operation and recovered well. Conclusions The exact incidence of extra-articular migrations of PEEK interference screws is unknown, but it seems to be quite low; despite this and its uncertain cause, the negative effects caused by the PEEK material need to be considered.

Abstract Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

Background Bone metastasis of prostate cancer (PCa) is a challenging problem, leading to poor prognosis of patients. Existing biomarkers have limited sensitivity and specificity. Therefore, we urgently need a novel diagnostic tool to predict PCa bone metastasis. Methods Patient data and blood samples were collected according to the inclusion and exclusion criteria. logistic regression analysis was used to screen clinical indicators and miRNAs, and radiomics was used to construct a prediction model. Finally, the performance of the model was evaluated by internal verification, external verification and Delong test. Two nomograms were successfully established by analyzing clinical data, plasma miRNAs and imaging data. Nomogram 1 predicts the presence or absence of bone metastasis; Nomogram 2 predicts whether the number of bone metastases is ≥ 4. Results Nomogram 1 constructed by tPSA, hsa-miR-548o-3p and radiomics had an AUC of 0.904. The AUC of the internal training set was 0.879, the internal test set was 0.956, and the AUC of the external data set was 0.877. The calibration curve and decision curve all performed well. Nomogram 2 constructed by ALP, hsa-miR-548o-3p and radiomics had an AUC of 0.849, with an AUC of 0.916 in the internal training set, 0.806 in the internal test set and 0.839 in the external data set. The calibration curve and decision curve showed good performance. Conclusions The combination of plasma exosomal miRNA and radiomics model has high reliability and accuracy in predicting the presence and number of bone metastases of PCa.

The aim of the present study was to assess the quality of recovery from anesthesia on patients subjected to laparoscopic radical resection of colorectal cancer under epidural block combined with general anesthesia or general anesthesia by means of Quality of Recovery-15 (QoR-15) questionnaire. Prospective randomized trial. The setting is at an operating room, a post-anesthesia care unit, and a hospital ward. Seventy patients, aging from 65 to 79 years with an American Society of Anesthesiologists physical status II or III, were scheduled to undergo laparoscopic radical resection of colorectal cancer. Epidural block combined with general anesthesia or general anesthesia. The QoR-15 was administered by an investigator blind to group allocation before surgery (T0), at 24 and 72h after surgery (T1 and T2), and on postoperative day 7 (T3). The quality of recovery, as assessed by the score on the QoR-15, was compared between the groups. Besides, the consumption of anesthetics, respiratory recovery time, response time, extubation time, flatus time, the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents, and the duration of the hospital stay were also recorded. The QoR-15 scores at T1 and T2 were significantly higher in the E + G group compared with the G group (P < 0.05). Among the five dimensions of the QoR-15, physiological comfort, physiological independence, pain, and emotional dimension were significantly better at T1 in the E + G group, and physiological comfort and pain were significantly better at T2 in the E + G group. This study demonstrates that epidural block combined with general anesthesia can improve the early recovery of elderly patients after laparoscopic radical resection of colorectal cancer from the perspective of patients.

Background Rotator cuff tear is a degenerative condition that has been previously linked to metabolic factors such as obesity and diabetes. However, the relationship between patients’ nutritional status and rotator cuff pathology remains unclear. Method We retrospectively reviewed data from patients with degenerative rotator cuff tears who underwent arthroscopic rotator cuff repair at our institution between June and December 2024. Collected variables included demographic characteristics, imaging findings, and biochemical markers indicative of nutritional status, such as hemoglobin, total lymphocyte count, serum albumin, prealbumin, and transferrin. The prognostic nutritional index (PNI) was calculated based on lymphocyte count and serum albumin levels. Patients were stratified based on the presence or absence of muscle atrophy and fatty infiltration, and intergroup comparisons were performed. Age-adjusted logistic regression was used to identify risk factors associated with muscle atrophy and fatty infiltration. Results A total of 109 patients met the inclusion criteria. Significant differences in age, obesity, hemoglobin, PNI, and albumin levels were observed between patients with and without muscle atrophy (all P  < 0.05). Similarly, age, obesity, hemoglobin, lymphocyte count, and albumin were significantly associated with fatty infiltration ( P  < 0.05). After adjusting for age, obesity was associated with lower odds of muscle atrophy (OR = 4.581) and fatty infiltration (OR = 4.178). Decreased hemoglobin levels were associated with increased risk of muscle atrophy (OR = 0.954) and fatty infiltration (OR = 0.968). Lower PNI was also associated with muscle atrophy (OR = 0.822) and fatty infiltration (OR = 0.801), and reduced serum albumin levels were linked to higher odds of both outcomes (OR = 0.785 and 0.815, respectively). Conclusion Obesity and poor nutritional status may be significant risk factors for muscle atrophy and fatty infiltration in patients with rotator cuff tears. Level of evidence Level IV.

A novel method of laser machining combined with high temperature chemical etching (LMHTCE) was proposed. This novel method can take full advantage of both approaches to drill film holes in an IN718 superalloy without a recast layer or a heat affect zone (HAZ). A solution of hydrochloric acid and sodium nitrate, which minimally reacts with IN718 at room temperature but rapidly reacts under high temperatures, was tested and chosen. Holes drilled in air, water, and chemical solutions by a pulsed laser of 1064 nm were studied, and scanning electron microscope (SEM) and energy dispersive spectrometer (EDS) were employed to detect the morphology of the holes and the elemental distribution in different zones. The holes processed in the chemical solution had fewer defects compared with those in the other two mediums. The defocusing distance parameter was optimized to minimize the hole diameter and taper. When the defocusing distance was 0 μm in the drilling stage and − 60 μm in the high temperature chemical etching stage, a hole with a smaller diameter and taper can be obtained.