Bifurcated Polymorphic Transition and Thermochromic Fluorescence of a Molecular Crystal Involving Three-Dimensional Supramolecular Gear Rotation.

The ability of molecules to move and rearrange in the solid state accounts for the polymorphic transition and stimuli-responsive properties of molecular crystals. However, how the crystal structure determines the molecular motion ability remains poorly understood. Here, we report that a three-dimensional (3D) supramolecular gear network in the green-emissive polymorph 1G of a dialkylamino-substituted anthracene-pentiptycene π-system (1) enables an unusual bifurcated polymorphic transition into a yellow-emissive polymorph (1Y) and a new green-emissive polymorph (1G*) via 3D correlated supramolecular rotation. The 90° forward correlated rotation causes the molecular conformation between the octyl and the anthracene units to change from syn to anti, the ladder-like supramolecular columns to constrict, and the gear network to disengage. This cooperative molecular motion is marked by the gradual formation of an intermediate state (1I) across the entire crystal from 170 to 230 °C, which then undergoes bifurcated (forward or backward rotation) and irreversible transitions to form polymorphs 1Y and 1G* at 230-235 °C. Notably, 1G* is similar to 1G but lacks gear engagement, preventing its transformation into 1Y. Nevertheless, 1G can be restored by grinding 1Y or 1G* or fuming with dichloromethane (DCM) vapor. This work illustrates the correlation between the crystal structure and solid-state molecular motion behavior and demonstrates how a 3D molecular gear system efficiently transmits thermal energy to drive the polymorphic transition and induce fluorochromism through significant conformational and packing changes.

Maternal and neonatal outcomes in women with congenital heart disease: A nationwide population-based study.

BACKGROUND: We evaluated the outcomes of pregnancy in women with congenital heart disease (CHD) and their offspring in Taiwan. We also investigated how different severity levels may influence the outcomes. METHODS: We used data (2009-2017) from the Birth Certificate Application database in Taiwan, which is linked to the National Health Insurance Research Database and Taiwan Maternal and Child Health Database. We identified 2990 women with CHD who had 4227 births. Based on the CHD subtypes, patients were further divided into "severe CHD" and "simple CHD" groups. RESULTS: Women with CHD have a significant risk of stillbirth. In maternal cardiac events, they had the highest risk of heart failure, followed by arrhythmia. The severity of CHD had a significant effect on the outcomes as well. The neonatal birth event that mothers with CHD have the highest risk of is preterm birth at < 32 weeks of gestation. The prominent difference in neonatal morbidities between mothers with severe and simple CHD is recurrent CHD in the offspring. The offspring of the severe CHD group had a higher risk of severe CHD, whereas those of the simple CHD group had a higher risk of simple CHD. CONCLUSION: During pregnancy, the monitoring of heart function and cardiac rhythm could be more intensive in mothers with CHD. In addition to accurately assessing fetal growth and development during antenatal care, mothers with severe CHD should be provided with careful fetal heart structure assessment and genetic testing along with counseling.

Strategies for subtyping primary aldosteronism.

Adrenal venous sampling (AVS) is a crucial method for the lateralization of primary aldosteronism (PA). It is advised to halt the use of the patient's antihypertensive medications and correct hypokalemia prior to undergoing AVS. Hospitals equipped to conduct AVS should establish their own diagnostic criteria based on current guidelines. If the patient's antihypertensive medications cannot be discontinued, AVS can be performed as long as the serum renin level is suppressed. The Task Force of Taiwan PA recommends using a combination of adrenocorticotropic hormone stimulation, quick cortisol assay, and C-arm cone-beam computed tomography to maximize the success of AVS and minimize errors by using the simultaneous sampling technique. If AVS is not successful, an NP-59 (131 I-6-ß-iodomethyl-19-norcholesterol) scan can be used as an alternative method to lateralize PA. We depicted the details of the lateralization procedures (mainly AVS, and alternatively NP-59) and their tips and tricks for confirmed PA patients who would consider to undergo surgical treatment (unilateral adrenalectomy) if the subtyping shows unilateral disease.

The growth factor multimodality on treating human dental mesenchymal stem cells: a systematic review.

BACKGROUND: Ensuring the quantity, quality, and efficacy of human dental mesenchymal stem cells (MSCs) has become an urgent problem as their applications increase. Growth factors (GFs) have low toxicity, good biocompatibility, and regulate stem cell survival and differentiation. They bind to specific receptors on target cells, initiating signal transduction and triggering biological functions. So far, relatively few studies have been conducted to summarize the effect of different GFs on the application of dental MSCs. We have reviewed the literature from the past decade to examine the effectiveness and mechanism of applying one or multiple GFs to human dental MSCs. Our review is based on the premise that a single dental MSC cannot fulfill all applications and that different dental MSCs react differently to GFs. METHODS: A search for published articles was carried out using the Web of Science core collection and PubMed. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. This review considered studies from 2014 to 2023 that examined the effects of GFs on human dental MSCs. The final selection of articles was made on the 15th of July 2023. RESULTS: Three thousand eight hundred sixty-seven pieces of literature were gathered for this systematic review initially, only 56 of them were selected based on their focus on the effects of GFs during the application of human dental MSCs. Out of the 56, 32 literature pieces were focused on a single growth factor while 24 were focused on multiple growth factors. This study shows that GFs can regulate human dental MSCs through a multi-way processing manner. CONCLUSION: Multimodal treatment of GFs can effectively regulate human dental MSCs, ensuring stem cell quality, quantity, and curative effects.

Syntactic Complexity and Frequency in the Neurocognitive Language System.

Prominent neurobiological models of language follow the widely accepted assumption that language comprehension requires two principal mechanisms: a lexicon storing the sound-to-meaning mapping of words, primarily involving bilateral temporal regions, and a combinatorial processor for syntactically structured items, such as phrases and sentences, localized in a left-lateralized network linking left inferior frontal gyrus (LIFG) and posterior temporal areas. However, recent research showing that the processing of simple phrasal sequences may engage only bilateral temporal areas, together with the claims of distributional approaches to grammar, raise the question of whether frequent phrases are stored alongside individual words in temporal areas. In this fMRI study, we varied the frequency of words and of short and long phrases in English. If frequent phrases are indeed stored, then only less frequent items should generate selective left frontotemporal activation, because memory traces for such items would be weaker or not available in temporal cortex. Complementary univariate and multivariate analyses revealed that, overall, simple words (verbs) and long phrases engaged LIFG and temporal areas, whereas short phrases engaged bilateral temporal areas, suggesting that syntactic complexity is a key factor for LIFG activation. Although we found a robust frequency effect for words in temporal areas, no frequency effects were found for the two phrasal conditions. These findings support the conclusion that long and short phrases are analyzed, respectively, in the left frontal network and in a bilateral temporal network but are not retrieved from memory in the same way as simple words during spoken language comprehension.

Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.

Background: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above. Methods: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review. Results: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient. Conclusion: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.

Incidence of hydrocephalus in traumatic brain injury: A nationwide population-based cohort study.

BACKGROUND: The aim of this study was to investigate the risk and peak time of post-traumatic hydrocephalus (PTH) in traumatic brain injury (TBI) patients with traumatic subarachnoid hemorrhage (SAH), compared to TBI patients without traumatic SAH. METHODS: In this retrospective population-based cohort study, the data was extracted from Longitudinal Health Insurance Database from 2000 to 2010 in Taiwan. A total of 23,775 TBI patients who had a first event TBI during 2000 to 2010 were included and divided into TBI with SAH (TBI-S) group and TBI without SAH (TBI-NS) group. We focused on analyzing the PTH in both groups within 2 years after brain injury. Competing risk regression models were performed to assess the risk of developing PTH in the TBI-S group compared to the TBI-NS group. RESULTS: Comparing to the TBI-NS group, there was a significantly higher cumulative incidence of PTH in the TBI-S group during the 2-year follow-up period. The adjusted hazard ratio (HR) of PTH in TBI-S group within 2 years was between 2.90-3.47, and the highest estimates were obtained within 6 months after injury (HR = 3.47, 95% CI: 2.43-4.94). The occurrence percentage of PTH was highest during 0-3rd month follow-up periods (1.95% in TBI-S group; 0.48% in TBI-NS group). CONCLUSIONS: The peak time of PTH occurrence was noted during 0-3rd month post brain injury. Traumatic SAH patients had an approximate 3-fold risk of developing PTH, comparing to TBI patients without traumatic SAH.

Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer.

Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti-lung cancer and anti-lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs.

Clinical and microbiological characteristics of recurrent group B streptococcal infection among non-pregnant adults.

OBJECTIVE: This study aimed to investigate the clinical and microbiological features of recurrent group B streptococcal (GBS) diseases among non-pregnant adults. METHODS: All hospitalized non-pregnant adults who had culture-proven GBS infections between January 2008 and December 2010 were enrolled in this retrospective study. Bacterial isolates were examined for their serotypes, genotypes, and antimicrobial resistance. RESULTS: The recurrence rate of GBS infection in Taiwan was found to be 9.3%. Of the 70 recurrent episodes in 32 patients, infections of the urinary tract (U) were diagnosed clinically in 55.7%, infections of the soft tissue (S) in 31.4%, and infections of the bloodstream (B) in 12.9%. The initial/recurrent episodes in 25 patients were mainly U/U (40.6%), followed by S/S (18.8%) and B/B (6.2%). The serotypes/serogroups identified were serotypes V (34.3%), Ib (22.9%), VI (17.1%), III (12.9%), IV (7.1%), and Ia (5.7%). Recurrent strains showed less resistance to erythromycin or clindamycin than non-recurrent strains. Six distinct genotypes were identified in 12 serotype VI isolates derived from seven patients; five of these isolate pairs had identical genotypes. CONCLUSIONS: Recurrent GBS diseases were found to occur considerably more often than previously thought, mainly in adults with a high comorbid index. Relapse, not new acquisition, was found to be more common.

Central diabetes insipidus in children with acute brain insult.

Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes.