Medial entorhinal cortex mediates learning of context-dependent interval timing behavior.

Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether they display learning dynamics required for encoding different temporal contexts. To explore this, we developed a new behavioral paradigm requiring mice to distinguish temporal contexts. Combined with methods for cellular resolution calcium imaging, we found that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we found that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we found evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience.

Functional studies on tandem carbohydrate-binding modules of a multimodular enzyme possessing two catalytic domains.

Although functional studies on carbohydrate-binding module (CBM) have been carried out extensively, the role of tandem CBMs in the enzyme containing multiple catalytic domains (CDs) is unclear. Here, we identified a multidomain enzyme (Lc25986) with a novel modular structure from lignocellulolytic bacterial consortium. It consists of a mannanase domain, two CBM65 domains (LcCBM65-1/LcCBM65-2), and an esterase domain. To investigate CBM function and domain interactions, full-length Lc25986 and its variants were constructed and used for enzymatic activity, binding, and bioinformatic analyses. The results showed that LcCBM65-1 and LcCBM65-2 both bind mannan and xyloglucan but not cellulose or ß-1,3-1,4-glucan, which differs from the ligand specificity of reported CBM65s. Compared to LcCBM65-2, LcCBM65-1 showed a stronger ligand affinity and a preference for acetylation sites. Both CBM65s stimulated the enzymatic activities of their respective neighboring CDs against acetylated mannan, but did not contribute to the activities of the distal CDs. The time course of mannan hydrolysis indicated that the full-length Lc25986 was more effective in the complete degradation of mixed acetyl/non-acetyl substrates than the mixture of single-CD mutants. When acting on complex substrates, LcCBM65-1 not only improved the enzymatic activity of the mannanase domain, but also directed the esterase domain to the acetylated polysaccharides. LcCBM65-2 adopted a low affinity to reduce interference with the catalysis of the mannanase domain. These results demonstrate the importance of CBMs for the synergism between the two CDs of a multidomain enzyme and suggest that they contribute to the adequate degradation of complex substrates such as plant cell walls. IMPORTANCE: Lignocellulolytic enzymes, particularly those of bacterial origin, often harbor multiple carbohydrate-binding modules (CBMs). However, the function of CBM multivalency remains poorly understood. This is especially true for enzymes that contain more than one catalytic domain (CD), as the interactions between CDs, CBMs, and CDs and CBMs can be complex. Our research demonstrates that homogeneous CBMs can have distinct functions in a multimodular enzyme. The tandem CBMs coordinate the CDs in catalytic conflict through their differences in binding affinity, ligand preference, and arrangement within the full-length enzyme. Additionally, although the synergism between mannanase and esterase is widely acknowledged, our study highlights the benefits of integrating the two enzymes into a single entity for the degradation of complex substrates. In summary, these findings enhance our understanding of the intra-synergism of a multimodular enzyme and emphasize the significance of multiple CBMs in this context.

Lipase in-situ immobilized in covalent organic framework: Enzymatic properties and application in the preparation of 1, 3-dioleoyl-2-palmitoylglycerol.

In this study, the critical importance of designing an appropriate immobilized carrier and method for free lipase to ensure exceptional biological catalytic activity and stability was emphasized. Covalent organic frameworks (COF-1) were synthesized as a novel porous carrier with an azine structure (-CN-NC-) through the condensation of hydrazine hydrate and benzene-1,3,5-tricarbaldehyde at room temperature. Simultaneously, Rhizomucor miehei lipase (RML) was immobilized within the COF-1 carrier using an in-situ aqueous phase method. Characterization of the carrier and RML@COF-1 and evaluation of the lipase properties of RML and RML@COF-1 through p-Nitrophenyl palmitate hydrolysis were conducted. Additionally, application in the synthesis of 1, 3-dioleoyl-2-palmitoylglycerol (OPO) was explored. The results showed that RML@COF-1 exhibited a high enzymatic loading of 285.4 mg/g. Under 60℃ conditions, the activity of RML@COF-1 was 2.31 times higher than that of free RML, and RML@COF-1 retained 77.25% of its original activity after 10 cycles of repeated use, indicating its excellent thermal stability and repeatability. Under the optimal conditions (10%, 1:8 PPP/OA, 45℃, 5 h), the yield of OPO reached 47.35%, showcasing the promising application prospects of the novel immobilized enzyme synthesized via in-situ aqueous phase synthesis for OPO preparation.

Medial entorhinal cortex plays a specialized role in learning of flexible, context-dependent interval timing behavior.

Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether MEC time cells display learning dynamics required for encoding different temporal contexts. To explore this, we developed a novel behavioral paradigm that requires distinguishing temporal contexts. Combined with methods for cellular resolution calcium imaging, we find that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we find that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we find evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience.

Research trends of acupuncture therapy on stress urinary incontinence from 1992 to 2022: A bibliometric analysis.

Background: Stress urinary incontinence (SUI), the most prevalent type of urinary incontinence disorder, has aroused increasing attention among societies since it has caused much inconvenience in daily life. In addition to conventional conservative treatments like medication and pelvic floor muscle training, acupuncture is now frequently advised. However, a bibliometric analysis of the trend of SUI therapies is still lacking. Objectives: This article was carried out using CiteSpace (6.3.1) software to research the use of acupuncture therapy on SUI worldwide over the past 30 years (since the database's inception). Methods: All related articles included were retrieved from the Web of Science Core Collection. CiteSpace (6.3.1) software was used to analyze the number of publications, countries and institutions, authors and cited authors, and burst keywords to assess the hotspots and trends over the previous three decades. And Microsoft Office Excel 2019 was also used for sorting data and generating tables. Results: The articles were retrieved on August 31, 2022. A total of 108 records with publication dates ranging from 1992 to 2022 were discovered. The annual number of publications generally increased. In the aspect of publication regions, the USA ranked first in centrality, but China had the largest number of publications. The China Academic of Chinese Medical Sciences, Beijing University of Chinese Medicine, and Shanghai University of Traditional Chinese Medicine were the top 3 institutions, according to the institution map. Liu Z (Liu ZS) was the most productive author, and Chen Y ranked first in the centrality. The article published by Liu Z (Liu ZS) in 2017 was the most cited reference. "Bladder neck suspension", "electrical stimulation" and "acupuncture" were popular therapies mentioned among the top ten hot topics. The keywords "therapy", "postprostatectomy incontinence", "muscle", "cell therapy", and "symptom" ranked in the top five on citation burst. The four frontier topics were "efficacy", "symptom", "cell therapy", and "medical technology". Conclusion: This study illustrated that the application of acupuncture on SUI had an increasing acceptance worldwide. Recent research has concentrated mainly on acupuncture and electroacupuncture, however, there is still not enough literature on these topics. The valuable information was provided for acupuncture researchers to identify prospects including potential collaborators, cooperation institutions, hot themes, and research frontiers.

Medial entorhinal cortex plays a specialized role in learning of flexible, context-dependent interval timing behavior.

In order to survive and adapt in a dynamic environment, animals must perceive and remember the temporal structure of events and actions across a wide range of timescales, including so-called interval timing on the scale of seconds to minutes1,2. Episodic memory (i.e. the ability to remember specific, personal events that occur in spatial and temporal context) requires accurate temporal processing and is known to require neural circuits in the medial temporal lobe (MTL), including medial entorhinal cortex (MEC)3-5. Recently, it has been discovered that neurons in MEC termed time cells, fire regularly at brief moments as animals engage in interval timing behavior, and as a population, display sequential neural activity that tiles the entire timed epoch6. It has been hypothesized that MEC time cell activity could provide temporal information necessary for episodic memories, yet it remains unknown whether the neural dynamics of MEC time cells display a critical feature necessary for encoding experience. That is, whether MEC time cells display context-dependent activity. To address this question, we developed a novel behavioral paradigm that requires learning complex temporal contingencies. Applying this novel interval timing task in mice, in concert with methods for manipulating neural activity and methods for large-scale cellular resolution neurophysiological recording, we have uncovered a specific role for MEC in flexible, context-dependent learning of interval timing behavior. Further, we find evidence for a common circuit mechanism that could drive both sequential activity of time cells and spatially selective neurons in MEC.

Clinical Study on the Treatment of Female Stress Urinary Incontinence With Modified Buzhong Yiqi Decoction.

Purpose: To study the clinical application value of Modified Buzhong Yiqi Decoction in the treatment of female stress urinary incontinence (SUI). Methods: A total of 103 female patients with SUI were included in this study, 13 were lost to follow-up, and the final number of studies was 90. General information about the patients, including age, years of menopause, body mass index (BMI), reproductive history, chronic respiratory disease, hypertension, and diabetes, were recorded. All the patients were treated with Modified Buzhong Yiqi Decoction alone for 4 weeks. The Patient Global Impression of Improvement (PGI-I), the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICI-QSF) and 72-h voiding diary were used to evaluate the patients' subjective symptoms and urinary incontinence degree before treatment, 1 month after treatment and 1 year after treatment, the efficacy and efficacy-related factors of Modified Buzhong Yiqi Decoction in the treatment of female SUI were analyzed. Results: One month after Modified Buzhong Yiqi Decoction treatment, compared with before treatment, the PGI-I questionnaire was very much better (68.89%), much better (8.89%), a little better (12.33%), no change (8.89%), the ICI-QSF score decreased (P < 0.05), and 72-h urine leakage frequency decreased (P < 0.05); One year after treatment compared with before treatment, the PGI-I questionnaire was very much better (40.00%), much better (17.78%), a little better (12.22%), no change (30.00%), the ICI-QSF score decreased (P < 0.05), and 72-h urine leakage frequency decreased (P < 0.05); and 1 year after treatment compared with 1 month after treatment, the ratio of very much better at 1 year after treatment was significantly decreased (P < 0.05), the score of the ICI-QSF was significantly increased (P < 0.05), and 72-h urine leakage frequency was significantly increased (P < 0.05). The correlation analysis showed that the efficacy at 1 month after treatment was negatively correlated with the severity of SUI and chronic respiratory diseases, but was not significantly correlated with age, menopause status, BMI, number of pregnancies, and number of births. The efficacy at 1 year after treatment was negatively correlated with the severity of SUI, chronic respiratory disease, age, and number of births and was positively correlated with BMI, but not significantly correlated with menopause status and number of pregnancies. Conclusion: Modified Buzhong Yiqi Decoction can effectively treat SUI in women. The efficacy is related to the severity of SUI and chronic abdominal hypertension, but the long-term efficacy decreases.

Thyroid metastasis from chondrosarcoma.

For chondrosarcoma, metastasis to the thyroid gland is extremely rare. The diagnosis and treatment of thyroid metastasis from chondrosarcoma are discussed here.We found a case of thyroid malignancy occurring after treatment of chondrosarcoma. We reviewed patient characteristics, histological presentations on initial chondrosarcoma and thyroid metastasis, treatments, times of recurrence and death. In addition, we searched Embase, PubMed, and ISI Web of Science databases (1996-2018) for articles published in the English language using the key words "chondrosarcoma" and "thyroid" and we reviewed almost all the reports about thyroid metastasis from chondrosarcoma.Only 5 cases of chondrosarcoma metastases in the thyroid gland have been reported in the literature. We found that most patients are adults, with compression signs or pain, most of whom have poor prognoses. The main examinations are ultrasound, CT and fine needle aspiration biopsy, and primary treatment is surgery.These rare cases of chondrosarcoma presenting as a metastasis in the thyroid gland highlight the importance of close communication between radiologists, histopathologists, and clinicians to ensure that such exceptional cases are not missed.

A high-resolution 3D epigenomic map reveals insights into the creation of the prostate cancer transcriptome.

To better understand the impact of chromatin structure on regulation of the prostate cancer transcriptome, we develop high-resolution chromatin interaction maps in normal and prostate cancer cells using in situ Hi-C. By combining the in situ Hi-C data with active and repressive histone marks, CTCF binding sites, nucleosome-depleted regions, and transcriptome profiling, we identify topologically associating domains (TADs) that change in size and epigenetic states between normal and prostate cancer cells. Moreover, we identify normal and prostate cancer-specific enhancer-promoter loops and involved transcription factors. For example, we show that FOXA1 is enriched in prostate cancer-specific enhancer-promoter loop anchors. We also find that the chromatin structure surrounding the androgen receptor (AR) locus is altered in the prostate cancer cells with many cancer-specific enhancer-promoter loops. This creation of 3D epigenomic maps enables a better understanding of prostate cancer biology and mechanisms of gene regulation.

Thyroid metastasis from non-small cell lung cancer.

Non-thyroid malignancies to the thyroid gland resulting from distant metastases are extremely rare, and such cases are rarely seen in clinical settings. The question of how a tumor metastasizes to the thyroid remains unanswered. Here we report a case of lung adenocarcinoma metastasizing to the thyroid gland. The article covers the pathological features, treatments, examination reports, and the postoperative follow-up reviews of the patient. In this article, we discuss the diagnostic method, the spread route, the prognosis, the mechanism and above all, the treatment. In addition, we searched the PubMed and ISI Web of Science databases for articles published in English using the key words "lung", "thyroid", and "metastasis", and we reviewed nearly all the reports about thyroid malignancies being metastasized from lung cancer. This rare case emphasizes the importance of the multifaceted comprehensiveness of the cephalometry diagnosis, pathological diagnosis, and immunohistochemical analysis to ensure that such rare cases are not missed. We declare that all cases of thyroid malignancies metastasized from the lungs shall be reported at large for further clinical research.

Highly specific phosphopeptide enrichment by titanium(IV) cross-linked chitosan composite.

Natural chitosan was applied as supporting material for Ti(IV) based immobilized metal ion affinity chromatographic (IMAC) material (Ti-CTS). Compared with other polymer based IMAC, Ti-CTS can save the cockamamie synthesis procedures and be easy to obtain. The morphology, surface area, pore volume and elemental composition of Ti-CTS were revealed by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) method and X-ray photoelectron spectroscopy (XPS). Tryptic digest products from several standard proteins and two real samples (non-fat milk and serum) were enriched using Ti-CTS to demonstrate the efficiency of this method. The results showed that this composite enables high sensitive and selective phosphopeptide enrichment from casein variants, non-fat milk and human serum. Furthermore, multi-phosphorylated peptides with three serine phospholated sites (S*S*S*) demonstrated high affinity to Ti-CTS. Hence, this method had great potential for future studies of complex phosphoproteomes and especially multi-phosphorylated peptides.