The Mid-Carnian Pluvial Episode (or “Carnian Wet Intermezzo”) interrupted the generally arid climate of the Triassic in different regions. An enhanced high-resolution time scale, especially with ...intercalibrated ammonoid, conodont and magnetic polarity zones, is required to understand the global coincidence of regional manifestations of this climatic change and possible causation factors. The termination of oolite-rich limestones and the initial influx of terrigenous debris at the Unit 1 to Unit 2 boundary in the Guanyinya and Qingyangou sections from Hanwang of the Sichuan Province, South China, are interpreted as a local shift from arid to humid climate. A detailed conodont sampling assigns this facies change to within the Mazzaella carnica range zone of the late Julian substage. Therefore, the conodont markers imply it is coeval with the onset of the mid-Carnian “ Rheingraben Event” at the Rappoltstein reference section in southern Germany; and ammonoids in that section enable correlation to the beginning of a negative carbon-isotope excursion that coincides with the termination of the Yangtze Platform at the Longchang reference section in Guizhou, South China. The first occurrence of Parapetella? guanyinensis sp. nov. is very close to the onset of the interpreted Carnian Pluvial Episode at Hanwang and to the cessation of widespread shallow-water carbonate facies in South China. In contrast to this “Intermezzo” episode in the West Tethys region, arid conditions did not resume in South China in the Eastern Tethys until long after the termination of this wet climate in late Julian.
•The termination of oolite-rich limestones is interpreted as a local shift from arid to humid climate.•The onset of the Mid-Carnian “Wet Intermezzo” Event is dated within the M. carnica range zone.•The onset of this humid episode appears to be synchronous with that in some European sections.•The first occurrence of Parapetella? guanyinensis sp. nov. is very close to the onset this humid episode.
Upper Triassic (Carnian) marine successions in the northwestern margin of Upper Yangtze Region (Sichuan Basin, China) show a lithological change from grey oolitic into a sponge-mound limestone (Units ...1 and 2 of the lower member of the Ma'antang Formation), then overlain by greyish black to dark grey sandy shale and siltstone (Units 3 and 4 of the upper member of the Ma'antang Formation). Siliceous sponge mounds were built by Hexactinellida, and this succession was examined in three localities: Jushui section in Anxian (JS), and Guanyinya (HWG) and Qingyangou sections (HWQ) in Hanwang, Mianzhu. The conodont Quadralella polygnathiformis confirms a Carnian age for the biolithite and oolitic limestone of the lower Ma'antang Formation. Abundant ammonoids identified as belonging to the Discotropitid and Juvavitid families suggest a Tuvalian 1 (early Late Carnian) age for the lowermost part of the greyish black sandy shale that overlies the sponge mound at the Jushui Section. Field investigations and microfacies analysis suggest that sponge mounds had two stages of growth in relatively deeper water with low energy. The first sponge-growth mound stage ended in a regional karstified omission surface, and was followed by a sudden increase of siliciclastic input. Greyish black shales containing plant fossils cover a second Upper Carnian sponge mound stage, which is mainly recorded in HWG. The onset of these shales may be related to the Carnian Pluvial Phase (CPP) documented in the western Tethys region (e.g., in Italy, Austria and Hungary). The demise of the sponge mounds at all three sections may have been triggered by the joint effect of climatic changes associated with the fresh water input caused by CPP and with a relative sea-level change caused by local tectonic movements in the course of the Indosinian orogeny.
In many tropical shallow water regions the end-Permian mass extinction event occurs at the top fossiliferous packstone beds and is immediately followed by the development of microbialite facies. Both ...the age and redox conditions of the microbialite have been debated and both factors are addressed here in a study of the Gaohua section (Cili County, Hunan Province, China): specifically the size distribution of pyrite framboids and high-resolution conodont biostratigraphy. The framboids populations show a broad size range with examples up to 30microns in diameter, and indicating dysoxic but not anoxic depositional conditions. More intense dysoxia is recorded in interbedded laminated micrites but not beds of giant ooids. Both the Hindeodus parvus zone and Isarcicella isarcica zones were established with the microbialite beds being confined to the H. parvus zone. Therefore, the formation of microbialite postdates the end Permian main mass extinction and records oxygen-poor conditions even in a shallow-water setting such as Gaohua section at Cili.
•The redox conditions of microbialite has been conducted by the size range of pyrite framboids on a Permian-Triassic section at Gaohua, Cili county, Hunan Province, South China, it is indicated that the microbialite was deposited in dysoxic condition but not anoxic condition.•High-resolution conodont biostratigraphy study enable the establishment of Hindeodus parvus zone and Isarcicella isarcica zone.•New conodont data reveals that the formation of microbialite postdates the end Permian main mass extinction rather than latest-Changshingian as previously thought.
Chimonobambusa hejiangensis (C.hejiangensis) is a high-quality bamboo species native to China, known for its shoots that are a popular nutritional food. Three C.hejiangensis cultivars exhibit unique ...color variation in their shoot sheaths, however, the molecular mechanism behind this color change remains unclear. We investigated flavonoid accumulation in the three bamboo cultivar sheaths using metabolomics and transcriptomics. UPLC-MS/MS identified 969 metabolites, with 187, 103, and 132 having differential accumulation in the yellow-sheath (YShe) vs. spot-sheath (SShe)/black-sheath (BShe) and SShe vs. BShe comparison groups. Flavonoids were the major metabolites that determined bamboo sheath color through differential accumulation of metabolites (DAMs) analysis. Additionally, there were 33 significantly differentially expressed flavonoid structural genes involved in the anthocyanin synthesis pathway based on transcriptome data. We conducted a KEGG analysis on DEGs and DAMs, revealing significant enrichment of phenylpropanoid and flavonoid biosynthetic pathways. Using gene co-expression network analysis, we identified nine structural genes and 29 transcription factors strongly linked to anthocyanin biosynthesis. We identified a comprehensive regulatory network for flavonoid biosynthesis which should improve our comprehension of the molecular mechanisms responsible for color variation and flavonoid biosynthesis in bamboo sheaths.
Abstract To date, earlier diagnosis of Alzheimer’s disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an ...upstream regulator of amyloid-beta (Aβ) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aβ plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of Aβ plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before Aβ plaque formation.
Obesity results from increased energy intake or defects in energy expenditure. Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. Peroxisome ...proliferator-activated receptor γ coactivator 1α (PGC1α) controls BAT-mediated thermogenesis by regulating the expression of
Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays an important role in cell proliferation and differentiation. We demonstrate a novel function of Id1 in BAT thermogenesis and programming of beige adipocytes in white adipose tissue (WAT). We found that adipose tissue-specific overexpression of
causes age-associated and high-fat diet-induced obesity in mice. Id1 suppresses BAT thermogenesis by binding to and suppressing PGC1α transcriptional activity. In WAT, Id1 is mainly localized in the stromal vascular fraction, where the adipose progenitor/precursors reside. Lack of Id1 increases beige gene and Ucp1 expression in the WAT in response to cold exposure. Furthermore, brown-like differentiation is increased in
-deficient mouse embryonic fibroblasts. At the molecular level, Id1 directly interacts with and suppresses Ebf2 transcriptional activity, leading to reduced expression of
, which determines beige/brown adipocyte cell fate. Overall, the study highlights the existence of novel regulatory mechanisms between Id1/PGC1α and Id1/Ebf2 in controlling brown fat metabolism, which has significant implications in the treatment of obesity and its associated diseases, such as diabetes.
The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, ...innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN.
We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework.
Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy.
Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.
The Nanpanjiang Basin is a key area for paleontological and biostratigraphical study of the Middle Triassic. Herein we studied Middle Triassic conodonts from a well-exposed section, the Shaiwa ...Section, which is located at the northwest end of the Nanpanjiang Basin. A total of six Anisian conodont zones are recognized; in ascending order, they are: the
Nicoraella germanica
Zone, the
Nicoraella kockeli
Zone, the
Paragondolella bulgarica
Zone, the
Neogondolella constricta
Zone, the
Neogondolella cornuta
Zone, and the
Paragondolella excelsa
Zone, respectively. The first occurrence of
Nicoraella kockeli
defines the Bithynian-Pelsonian boundary. The Pelsonian-Illyrian boundary is defined by the first occurrence of
Neogondolella constricta
. The Anisian-Ladinian boundary cannot be recognized at the Shaiwa Section due to the absence of conodont indicative of the Ladinian. However, the new conodont data indicate that the uppermost strata could be very close to the boundary. The abrasion of conodont surfaces provides evidence for demonstrating reworking at the Shaiwa Section, which makes some conodonts possess a longer stratigraphic range than previously recorded. The variation in relative abundance between blade-shaped conodonts and platform conodonts indicates that segminiplanate elements probably preferred deeper and oxygenated environments whereas a restricted marine environment is more suitable for segminate elements.
Tumor residue after concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients often predicts poor prognosis. Thus, the objective of this retrospective study is to develop a ...nomogram that combines magnetic resonance (MRI) radiomics features and clinical features to predict the early response of locally advanced nasopharyngeal carcinoma (LA-NPC).
A total of 91 patients with LA-NPC were included in this study. Patients were randomly divided into training and validation cohorts at a ratio of 3:1. Univariate and multivariate analyses were performed on the clinical parameters of the patients to select clinical features to build a clinical model. In the training cohort, the Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to select radiomics features for construction of a radiomics model. The logistic regression algorithm was then used to combine the clinical features with the radiomics features to construct the clinical radiomics nomogram. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical radiomics nomogram.
Platelet lymphocyte ratio (PLR) and nasopharyngeal tumor volume were identified as independent predictors of early response in patients with locally advanced nasopharyngeal carcinoma. A total of 5502 radiomics features were extracted, from which 25 radiomics features were selected to construct the radiomics model. The clinical radiomics nomogram demonstrated the highest AUC in both the training and validation cohorts (training cohort 0.975 vs 0.973 vs 0.713; validation cohort 0.968 vs 0.952 vs 0.706). The calibration curve and DCA indicated good predictive performance for the nomogram.
A clinical radiomics nomogram, which combines clinical features with radiomics features based on MRI, can predict early tumor regression in patients with LA-NPC. The performance of the nomogram is superior to that of either the clinical model or radiomics model alone. Therefore, it can be used to identify patients without CR at an early stage and provide guidance for personalized therapy.
The δ-opioid receptor (δOR) has been considered as a therapeutic target in multiple neurological and neuropsychiatric disorders particularly as δOR agonists are deemed safer alternatives relative to ...the more abuse-liable µ-opioid receptor drugs. Clinical development of δOR agonists, however, has been challenging in part due to the seizure-inducing effects of certain δOR agonists. Especially agonists that resemble the δOR-selective agonist SNC80 have well-established convulsive activity. Close inspection suggests that many of those seizurogenic δOR agonists efficaciously recruit β-arrestin, yet surprisingly, SNC80 displays enhanced seizure activity in β-arrestin 1 knockout mice. This finding led us to hypothesize that perhaps β-arrestin 1 is protective against, whereas β-arrestin 2 is detrimental for δOR-agonist-induced seizures. To investigate our hypothesis, we characterized three different δOR agonists (SNC80, ADL5859, ARM390) in cellular assays and
in vivo
in wild-type and β-arrestin 1 and β-arrestin 2 knockout mice for seizure activity. We also investigated downstream kinases associated with β-arrestin-dependent signal transduction. We discovered that δOR agonist-induced seizure activity strongly and positively correlates with β-arrestin 2 efficacy for the agonist, but that indirect inhibition of ERK activation using the MEK inhibitor SL327 did not inhibit seizure potency and duration. Inhibition of the PI3K/AKT/mTOR signaling with honokiol but not PQR530, attenuated SNC80 seizure duration in β-arrestin 1 knockout, but honokiol did not reduce SNC80-induced seizures in wild-type mice. Ultimately, our results indicate that β-arrestin 2 is correlated with δOR agonist-induced seizure intensity, but that global β-arrestin 1 knockout mice are a poor model system to investigate their mechanism of action.
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