bluuebunny/crossref_metadata_2025 huggingface dataset:
Deoxyshikonin: a promising lead drug grass against drug resistance or sensitivity to
Helicobacter pylori
in an acidic environment
Authors: Xu Jia-yin , Dong Hui-hua , Liao Li-juan , Yang Shi-xian , Wang Lu-yao , Chen Hao , Luo Peipei , Huang Liang , Guan Ai-xing , Huang Yan-Qiang
Published: August 2024

Helicobacter pylori
(
H. pylori
) is closely associated with the diseases such as gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug resistance is very severe, and new antibiotics are urgently needed. Nine comfrey compounds were screened by antimicrobial susceptibility testing, among which deoxyshikonin had the best inhibitory effect, with a minimum inhibitory concentration (MIC) of 0.5–1 µg/mL. In addition, deoxyshikonin also has a good antibacterial effect in an acidic environment, it is highly safe, and
H. pylori
does not readily develop drug resistance. Through
in vivo
experiments, it was proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute gastritis in mice infected with the multidrug-resistant
H. pylori
BS001 strain. After treatment with desoxyshikonin, colonization of
H. pylori
in the gastric mucosa of mice was significantly reduced, gastric mucosal damage was repaired, inflammatory factors were reduced, and the treatment effect was better than that of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to solve the difficulty of drug resistance in
H. pylori
, and its antibacterial mechanism may be to destroy the biofilm and cause an oxidation reaction.
An approach to analyze spatiotemporal patterns of gene expression at single-cell resolution in
Candida albicans
-infected mouse tongues
Authors: Lindemann-Perez Elena , Rodríguez Diana L. , Pérez J. Christian
Published: August 2024

Microbial gene expression measurements derived from infected organs are invaluable to understand pathogenesis. However, current methods are limited to “bulk” analyses that neglect microbial cell heterogeneity and the lesion's spatial architecture. Here, we report the use of hybridization chain reaction RNA fluorescence
in situ
hybridization (HCR RNA-FISH) to visualize and quantify
Candida albicans
transcripts at single-cell resolution in tongues of infected mice. The method is compatible with fixed-frozen and formalin-fixed paraffin-embedded tissues. We document cell-to-cell variation and intriguing spatiotemporal expression patterns for
C. albicans
mRNAs that encode products implicated in oral candidiasis. The approach provides a spatial dimension to gene expression analyses of host-
Candida
interactions.

IMPORTANCE

Candida albicans
is a fungal pathobiont inhabiting multiple mucosal surfaces of the human body. Immunosuppression, antibiotic-induced microbial dysbiosis, or implanted medical devices can impair mucosal integrity enabling
C. albicans
to overgrow and disseminate, causing either mucosal diseases such as oropharyngeal candidiasis or life-threatening systemic infections. Profiling fungal genes that are expressed in the infected mucosa or in any other infected organ is paramount to understand pathogenesis. Ideally, these transcript profiling measurements should reveal the expression of any gene at the single-cell level. The resolution typically achieved with current approaches, however, limits most gene expression measurements to cell population averages. The approach described in this report provides a means to dissect fungal gene expression in infected tissues at single-cell resolution.
Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance
Authors: Lu Qinwei , Zhu Rongtao , Zhou Lin , Zhang Ruifang , Li Zhen , Xu Peng , Wang Zhiwei , Wu Gang , Ren Jianzhuang , Jiao Dechao , Song Yan , Li Jian , Wang Weijie , Liang Ruopeng , Ma Xiuxian , Sun Yuling
Published: August 2024

Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (
N
case
= 140,
N
control
= 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients’ gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including
Prevotella
, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased
Prevotella
in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.

IMPORTANCE

This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore,
Prevotella
may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.
Comprehensive evaluation of primer pairs targeting the ammonia monooxygenase subunit A gene of complete ammonia-oxidizing
Nitrospira
Authors: Blom Pieter , Smith Garrett J. , van Kessel Maartje A. H. J. , Koch Hanna , Lücker Sebastian
Published: August 2024

Since the discovery of complete ammonia oxidizers (comammox) within the genus
Nitrospira
, their distribution and abundance across habitats have been intensively studied to better understand their ecological significance. Many primers targeting their ammonia monooxygenase subunit A gene (
amoA
) have been designed to detect and quantify comammox bacteria and to describe their community structure. We identified 38 published primers, but only few had high coverage and specificity for all known comammox
Nitrospira
or one of the two described subclades. For each target group, we comprehensively evaluated selected primer pairs using
in silico
analyses, endpoint PCRs, qPCRs, and amplicon sequencing on samples from various environments. Endpoint PCRs and qPCRs showed that the most commonly used primer pairs (comaA-244F/659R, comaB-244F/659R, and Ntsp-amoA162F/359R) produced several bands, which likely inflated quantifications via qPCR. In contrast, the recently published primer combinations CA377F/C576R, CB377F/C576R, and CA-CB377F/C576R resulted mostly in a single band. Furthermore, amplicon sequencing demonstrated that these primer combinations also captured the highest richness of comammox
Nitrospira
. Taken together, our results indicate that few existing comammox
amoA
primer combinations have both high specificity and coverage and that the choice of these high-specificity and high-coverage primer pairs substantially impacts the accurate detection, quantification, and community description of comammox bacteria. We, therefore, recommend using the CA377F/C576R, CB377F/C576R, and CA-CB377F/C576R primer pairs.

IMPORTANCE

Bacteria that can fully convert ammonia via nitrite to nitrate, the complete ammonia oxidizers (comammox), were recently discovered and are found in many natural and engineered environments. PCR-based tools to study their abundance and diversity were rapidly developed, resulting in a plethora of primers available, many of which are widely used. The presence of comammox bacteria in an environment can, however, only be correctly determined if the used primers detect all members of this group while not detecting any other guilds. This study assesses the coverage and specificity of existing primers targeting comammox bacteria using both computational and standard molecular techniques, revealing large differences in their performance. The uniform usage of well-performing primers across studies could aid in generating comparable and generalizable data to better understand the importance of comammox bacteria in the environment.
Whole genome analysis of multidrug-resistant
Escherichia coli
isolate collected from drinking water in Armenia revealed the plasmid-borne
mcr-1.1-
mediated colistin resistance
Authors: Karpenko Anna , Shelenkov Andrey , Manzeniuk Igor , Kulikova Nina , Gevorgyan Arman , Mikhaylova Yulia , Akimkin Vasiliy
Published: August 2024

The rate of polymyxin-resistant
Enterobacteriaceae
, as well as human and animal infections caused by them, is increasing worldwide, posing a high epidemiological threat since colistin represents a last-resort antibiotic to treat complicated infections. The study of environmental niches, in particular, aquatic ecosystems in terms of genome analysis of inhabiting antimicrobial-resistant (AMR) microorganisms as reservoirs of acquired resistance determinants (AMR genes), represents a specific concern from a One Health approach. Here, we present a phenotypic AMR analysis and molecular characterization of
Escherichia coli
isolate found in municipal drinking water after an accident in the water supply system of a residential building in Armenia in 2021. CrieF1144
E. coli
isolate was resistant to ampicillin, ampicillin/sulbactam, cefuroxime, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, colistin, and tigecycline, whereas whole genome sequencing (WGS) revealed
blaTEM-1B
,
tet(A
), and a combination of
dfrA14
with
sul1
resistance determinants, which corresponds well with phenotypic resistance above. Moreover, the multidrug-resistant isolate studied harbored
mcr-1.1
gene on a conjugative 251 Kb IncHI2 plasmid, whose structure was determined using hybrid short- and long-reads assembly. CrieF1141_p1 plasmid carried all antimicrobial resistance genes revealed in the isolate and did not harbor any virulence determinants, so it could contribute to the spread of AMR genes in the bacterial population. Two copies of ISApl1 transposase-encoding element, which is likely to mediate
mcr-1.1
gene mobilization, were revealed surrounding this gene in a plasmid.

IMPORTANCE

Evolutionary patterns of
Escherichia coli
show that they usually develop into highly pathogenic forms by acquiring fitness advantages such as antimicrobial resistance (AMR) and various virulence factors through horizontal gene transfer mediated by mobile elements. This has led to high prevalence of multidrug-resistant (MDR) strains, which highlights the relevancy of enhanced surveillance to monitor and prevent transmission of the MDR bacteria to human and animal populations. However, the limited number of reports regarding the whole genome sequencing (WGS) investigation of MDR
E. coli
strains isolated from drinking water and harboring
mcr
genes hampers the adoption of a comprehensive approach to address the relationship between environmental
E. coli
populations and human and veterinary infections. Our results highlight the relevance of analyzing the environment, especially water, as a part of the surveillance programs to understand the origins and dissemination of antimicrobial resistance within the One Health concept.
Clostridioides difficile
exploits xanthine and uric acid as nutrients by utilizing a selenium-dependent catabolic pathway
Authors: Johnstone Michael A. , Self William T.
Published: August 2024

Selenium is a trace element that plays critical roles in redox biology; it is typically incorporated into “selenoproteins” as the 21st amino acid selenocysteine. Additionally, selenium exists as a labile non-selenocysteine cofactor in a small subset of selenoproteins known as selenium-dependent molybdenum hydroxylases (SDMHs). In purinolytic clostridia, SDMHs are implicated in the degradation of hypoxanthine, xanthine, and uric acid for carbon and nitrogen. While SDMHs have been biochemically analyzed, the genes responsible for the insertion and maturation of the selenium cofactor lack characterization. In this study, we utilized the nosocomial pathogen
Clostridioides difficile
as a genetic model to begin characterizing this poorly understood selenium utilization pathway and its role in the catabolism of host-derived purines. We first observed that
C. difficile
could utilize hypoxanthine, xanthine, or uric acid to overcome a growth defect in a minimal medium devoid of glycine and threonine. However, strains lacking selenophosphate synthetase (
selD
mutants) still grew poorly in the presence of xanthine and uric acid, suggesting a selenium-dependent purinolytic process. Previous computational studies have identified
yqeB
and
yqeC
as potential candidates for cofactor maturation, so we subsequently deleted each gene using CRISPR-Cas9 technology. We surprisingly found that the growth of the Δ
yqeB
mutant in response to each purine was similar to the behavior of the
selD
mutants, while the Δ
yqeC
mutant exhibited no obvious phenotype. Our results suggest an important role for YqeB in selenium-dependent purine catabolism and also showcase
C. difficile
as an appropriate model organism to study the biological use of selenium.

IMPORTANCE

The apparent modification of bacterial molybdenum hydroxylases with a catalytically essential selenium cofactor is the least understood mechanism of selenium incorporation. Selenium-dependent molybdenum hydroxylases play an important role in scavenging carbon and nitrogen from purines for purinolytic clostridia. Here, we used
Clostridioides difficile
as a genetic platform to begin dissecting the selenium cofactor trait and found genetic evidence for a selenium-dependent purinolytic pathway. The absence of
selD
or
yqeB
—a predicted genetic marker for the selenium cofactor trait—resulted in impaired growth on xanthine and uric acid, known substrates for selenium-dependent molybdenum hydroxylases. Our findings provide a genetic foundation for future research of this pathway and suggest a novel metabolic strategy for
C. difficile
to scavenge host-derived purines from the gut.
Successful pregnancy in Takayasu’s arteritis type III with complete infrarenal aortic block
Authors: Sankarappan Priya , Tejanaik Parvathi , Sagili Haritha
Published: August 2024

A Gravida 2 Para 1 Live 1 in her late 20s and of South Asian ethnicity with previous lower segment caesarean section (LSCS) was hospitalised for confinement at 37 weeks for chronic hypertension with superimposed pre-eclampsia.The patient was diagnosed with type III Takayasu’s arteritis following a previous uncomplicated pregnancy. A year after her first childbirth, she presented with headache, recurrent scleritis, hypertension, bilateral absent lower limb pulses and right femoral bruit. CT angiogram revealed concentric thickening of the aorta and complete occlusion of the infrarenal aorta, with a saccular aneurysm 18 mm in diameter in the distal thoracic aorta at the T10 level. She was started on immunosuppressants and antihypertensives. During the current pregnancy, she received multidisciplinary care and underwent an elective LSCS with intrauterine contraceptive device (IUCD) placement at term under spinal anaesthesia. Postoperatively, nitroglycerine infusion followed by oral labetalol was administered for hypertension. She was discharged on day 10 with regular follow-up.
Unwashed grapes as a cause of organophosphate poisoning in a child in rural India
Authors: Patil Mallanagouda M , Doddihal Chandrika R , Sinha Anwita , Kumar BM Prasanna
Published: August 2024

This report describes the symptoms of pesticide poisoning in a previously healthy teenage girl. After consuming unwashed grapes for several days, the girl developed the following symptoms: drowsiness, vomiting, truncal weakness and fasciculations in the tongue and hands. Blood tests confirmed exposure to a small amount of the organophosphate (OP) compound, a type of chemical found in certain pesticides. The girl was treated with supportive care and cholinesterase reactivators, which minimised the damage caused by OP poisoning. Within 48 hours, the girl’s symptoms improved and she made a full recovery. This case highlights that OP poisoning can present without classic cholinergic crisis symptoms (SLUDGING), including miosis. Fasciculations, as observed in this case, are a significant clue to the diagnosis.
Airway consequences of alendronic acid aspiration
Authors: Lonsdale Henry , Sawant Rupali , Kinshuck Andrew , Fleming Jason
Published: August 2024

Bisphosphonates are commonly prescribed medications to prevent and treat osteoporosis. Although possessing low side effect profiles, the potential for severe topical effects is rare but important. Irritation of the upper gastrointestinal tract is well documented; however, the risk and effects of accidental aspiration are rarely reported.

Attention is drawn to a case recently managed at a tertiary head and neck centre where a patient in their 70s was admitted in respiratory distress 3 days after aspirating alendronic acid. This case highlights the potential risk of topical chemical injury posed to the airway by bisphosphonates.

Bisphosphonates should be prescribed with detailed and specific counselling regarding this risk. Pharmacological product literature should be updated to reflect the risk. Clinical teams should be aware of and vigilant for the delayed presentation and prolonged symptom course of such injuries. Prompt airway intervention and techniques to minimise further mucosal trauma ensure optimal outcomes.
Large language models: a new frontier in paediatric cataract patient education
Authors: Dihan Qais , Chauhan Muhammad Z , Eleiwa Taher K , Brown Andrew D , Hassan Amr K , Khodeiry Mohamed M , Elsheikh Reem H , Oke Isdin , Nihalani Bharti R , VanderVeen Deborah K , Sallam Ahmed B , Elhusseiny Abdelrahman M
Published: August 2024

Background/aims

This was a cross-sectional comparative study. We evaluated the ability of three large language models (LLMs) (ChatGPT-3.5, ChatGPT-4, and Google Bard) to generate novel patient education materials (PEMs) and improve the readability of existing PEMs on paediatric cataract.

Methods

We compared LLMs’ responses to three prompts. Prompt A requested they write a handout on paediatric cataract that was ‘easily understandable by an average American.’ Prompt B modified prompt A and requested the handout be written at a ‘sixth-grade reading level, using the Simple Measure of Gobbledygook (SMOG) readability formula.’ Prompt C rewrote existing PEMs on paediatric cataract ‘to a sixth-grade reading level using the SMOG readability formula’. Responses were compared on their quality (DISCERN; 1 (low quality) to 5 (high quality)), understandability and actionability (Patient Education Materials Assessment Tool (≥70%: understandable, ≥70%: actionable)), accuracy (Likert misinformation; 1 (no misinformation) to 5 (high misinformation) and readability (SMOG, Flesch-Kincaid Grade Level (FKGL); grade level <7: highly readable).

Results

All LLM-generated responses were of high-quality (median DISCERN ≥4), understandability (≥70%), and accuracy (Likert=1). All LLM-generated responses were not actionable (<70%). ChatGPT-3.5 and ChatGPT-4 prompt B responses were more readable than prompt A responses (p<0.001). ChatGPT-4 generated more readable responses (lower SMOG and FKGL scores; 5.59±0.5 and 4.31±0.7, respectively) than the other two LLMs (p<0.001) and consistently rewrote them to or below the specified sixth-grade reading level (SMOG: 5.14±0.3).

Conclusion

LLMs, particularly ChatGPT-4, proved valuable in generating high-quality, readable, accurate PEMs and in improving the readability of existing materials on paediatric cataract.
Impact of multiple obesity metrics on hypertensive disorders of pregnancy: a meta-analysis and Mendelian randomisation study
Authors: Sun Mengting , Gao Ming , Luo Manjun , Wang Tingting , Ruan Xiaorui , Tang Jiapeng , Chen Qian , Liu Hanjun , Li Liuxuan , Qin Jiabi
Published: August 2024

Background

The relationships between various obesity measures and hypertensive disorders of pregnancy (HDP) remain inadequately explored, and their causal links are not well understood. This study aims to clarify these associations and investigate the mediating role of triglycerides.

Methods

We conducted a comprehensive meta-analysis of observational studies alongside Mendelian randomisation (MR) analysis to assess the impact of 10 obesity measures on HDP risk. Additionally, we evaluated the mediating effect of triglycerides.

Results

Our meta-analysis revealed significant associations between maternal prepregnancy overweight/obesity and increased risks of gestational hypertension (GH) (overweight: OR=1.98, 95% CI 1.83 to 2.15; obesity: OR=3.77, 95% CI 3.45 to 4.13) and pre-eclampsia (overweight: OR=1.78, 95% CI 1.67 to 1.90; obesity: OR=3.46, 95% CI 3.16 to 3.79). Higher maternal waist circumference (WC) was also linked to increased pre-eclampsia risk (OR=1.45, 95% CI 1.14 to 1.83). MR analyses indicated that each 1-SD increase in genetically predicted obesity measures (whole body fat mass, body fat percentage, trunk fat mass, trunk fat percentage, body mass index, WC, hip circumference) was associated with higher risks of GH and pre-eclampsia. Triglycerides mediated 4.3%–14.1% of the total genetic effect of these obesity measures on GH and pre-eclampsia risks.

Conclusions

This study demonstrates that various obesity measures are causally linked to increased HDP risk and highlights the mediating role of triglycerides. These findings could inform clinical practices and public health strategies aimed at reducing HDP through targeted obesity and triglyceride management.
Counting $$U(N)^{\otimes r}\otimes O(N)^{\otimes q}$$ invariants and tensor model observables
Authors: Avohou Remi Cocou , Ben Geloun Joseph , Toriumi Reiko
Published: August 2024

$$U(N)^{\otimes r} \otimes O(N)^{\otimes q}$$

U

(
N
)

⊗
r

⊗
O

(
N
)

⊗
q

invariants are constructed by contractions of complex tensors of order $$r+q$$

r
+
q

, also denoted (r, q). These tensors transform under r fundamental representations of the unitary group U(N) and q fundamental representations of the orthogonal group O(N). Therefore, $$U(N)^{\otimes r} \otimes O(N)^{\otimes q}$$

U

(
N
)

⊗
r

⊗
O

(
N
)

⊗
q

invariants are tensor model observables endowed with a tensor field of order (r, q). We enumerate these observables using group theoretic formulae, for tensor fields of arbitrary order (r, q). Inspecting lower-order cases reveals that, at order (1, 1), the number of invariants corresponds to a number of 2- or 4-ary necklaces that exhibit pattern avoidance, offering insights into enumerative combinatorics. For a general order (r, q), the counting can be interpreted as the partition function of a topological quantum field theory (TQFT) with the symmetric group serving as gauge group. We identify the 2-complex pertaining to the enumeration of the invariants, which in turn defines the TQFT, and establish a correspondence with countings associated with covers of diverse topologies. For $$r>1$$

r
>
1

, the number of invariants matches the number of (q-dependent) weighted equivalence classes of branched covers of the 2-sphere with r branched points. At $$r=1$$

r
=
1

, the counting maps to the enumeration of branched covers of the 2-sphere with $$q+3$$

q
+
3

branched points. The formalism unveils a wide array of novel integer sequences that have not been previously documented. We also provide various codes for running computational experiments.
Recent improvements in the novel approach to the fast detection of surface contaminations
Authors: Wilsenack Frank , Meyer Fabian , Flores Yuri V. , Haertelt Marko , Adelhardt Mario , Ficks Arne
Published: August 2024

Here, we present the idea behind a novel measurement system and the recent improvements in detecting surface contaminations using a tunable, very fast three-core quantum cascade laser (QCL) system. It is developed as a potential replacement for the old established double-wheel sampling system currently used to detect surface threats caused by hazardous, non-volatile chemical substances. The novel system design is based on an optical measurement principle, allowing standoff detection and identification, thus rendering ground contact unnecessary. One of the leading military requirements for a CBRN reconnaissance vehicle is a high marching speed; hence, this new system is designed to have an ultra-short acquisition time and an adequate spectral bandwidth for measurements in the mid-infrared (MIR). This innovative approach may replace the more cumbersome indirect detection techniques. We discuss the main advantages and evaluate possible application scenarios that we expect from this setup. Active IR backscatter spectroscopy generally permits the contactless identification of hazardous chemical substances on surfaces. Here, the design was optimized around an approximate measuring distance of decimeters. Using a monoaxial setup, the autofocus is less demanding than alternative approaches and even allows for rapid measurements of rough surfaces. We built the improved measurement system based on novel QCL modules that integrate micro-opto-electro-mechanical grating scanners (MOEMS) in an external cavity. These elaborate laser modules provide almost one kilohertz (kHz) spectral scan speeds and typically cover a spectral range of 200–300 cm-1, respectively. Furthermore, such modules achieve measurement times of as short as one millisecond per spectrum. The full spectral coverage of the system is realized by coupling several of such modules.
Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway
Authors: Zhang Ning-Xin , Guan Chen , Li Chen-Yu , Xu Ling-Yu , Xin Yan-Lu , Song Zhuo , Li Tian-Yang , Yang Cheng-Yu , Zhao Long , Che Lin , Wang Yan-Fei , Man Xiao-Fei , Xu Yan
Published: August 2024

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-1β) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.
Tax avoidance and earnings management: Evidence from French firms
Authors: Hlel Khawla
Published: August 2024

In France, accounting regulations and tax legislation follow separate paths. Thus, the areas of nonconformity between financial accounting standards and tax laws can create opportunities for firms to engage in opportunistic behaviors. For instance, they may manipulate earnings in order to minimize tax liabilities while still presenting favorable financial results to stakeholders. This gives us an opportunity to investigate the nature of the relationship between tax avoidance (TA) and earnings management. Using a sample of 323 French firms over the period 2010–2017, we provide evidence that there is a positive simultaneous relationship between TA and earnings management. Consistent with agency theory and political-contractual perspectives, our empirical results highlight that discrepancies between accounting standards and tax laws can impact reporting practices, potentially leading to a portrayal of a more favorable financial position than the actual reality. Besides, our finding suggests that owing to the fact that French firms operate in an environment that allows substantial discretion in their financial and tax accounting decision, they could, therefore, have a greater ability to be aggressive for both financial and tax reporting purposes. Hence, it is recommended that regulators minimize the discretion in financial and tax standards. Additionally, this study will be useful for investors to adopt a higher degree of monitoring in order to reduce managerial opportunistic behavior.
Quantifying the Impact of Microstructure Variation on Charging Capability in Lithium-Ion Batteries
Authors: Teel Hunter , Garrick Taylor R. , Sepe Mitchell A. , Lopata Joseph S. , Srinivasan Srikant , Wang Fengkun , Zeng Yangbing , Shimpalee Sirivatch
Published: August 2024

Through the use of electrochemical simulations, variation in the local onset of lithium plating can be predicted and used to set charging guidelines to reduce the risk of lithium plating. The pseudo-two-dimensional (P2D) model is typically used for capturing this behavior; however, it only provides a global lithium plating onset estimate and does not consider the local variation. With material properties translated to an average continuum value, the P2D model can simulate rapid charge and capture global onset of lithium plating. However, this model lacks the ability to resolve localized behaviors across individual components due to local non-uniformities. Our three-dimensional microstructure-based (3DMS) modeling method that we employ to simulate rapid charge and capture local performance across the electrochemical components while agreeing with P2D model. Using the 3DMS model, we predict the onset of local lithium plating to design more conservative charging conditions to delay the onset of lithium plating and improve the performance of these electrochemical systems. In this work, several similar microstructures are evaluated for the lithium plating onset time during fast charge operation. A small normal distribution for particle sizes are explored to drive variation in performance and are compared to a uniform particle size structure.
Electrochemical Riboflavin Detection Using 2D Nanoflake–Like CuO Nanostructure Modified Electrodes
Authors: Ahmad Rafiq , Khan Marya , Abdullah  , Rehman Md. Tabish , AlAjmi Mohamed F. , Alam Shamshad , Mishra Prabhash , Lee Byeong-Il
Published: August 2024

Two-dimensional (2D) nanostructures are valued for their ultrathin planar surface and high charge carrier mobility, which offer enhanced sensing capabilities. Herein, we synthesised 2D nanoflake–like copper oxide (CuO) nanostructures using a hydrothermal method for electrochemical riboflavin sensor fabrication. Electrochemical analysis of nanoflake–like CuO modified glassy carbon electrode (GCE) was analysed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The differential pulse voltammetry (DPV) technique was used for testing the electrochemical sensing performance of the fabricated riboflavin sensor. The designed sensor detected riboflavin in concentrations ranging from 10 to 1250 nM with a high sensitivity (571.8 μA/μM cm2) and a limit of detection (LOD) of 6.5 nM. The sensor’s excellent electrocatalytic activity towards riboflavin is primarily attributed to the unique CuO nanoflake–like morphology that provides a high surface area. Furthermore, sensors showed excellent selectivity, reproducibility, and stability, essential attributes for precise riboflavin detection and long-term usage. Overall, the electrochemical sensor based on nanoflake–like CuO nanostructures represents a promising platform for sensitive riboflavin detection. An easy synthesis of 2D nanoflake–like CuO nanostructures provides the possibility of future potential applications of these nanomaterials in analytical chemistry domains such as biomedical diagnostics, food analysis, and environmental monitoring.
Thermal Performance of a Cylindrical Li[Ni0.6Co0.2Mn0.2]O2/Graphite Battery based on the Electrochemical-Thermal Coupling Model
Authors: Zhang Chao , Shang Jin , Xiong Yonglian , Yi Ting , Hou Quanhui , Qian Xing
Published: August 2024

The thermal safety of lithium-ion batteries has garnered significant attention due to its pivotal role in the field of new energy. In this work, a three-dimensional electrochemical-thermal coupling model based on the P2D model was established for predicting the thermal performance. The charge-discharge and temperature rise experiments via 18650 cylindrical Li[Ni0.6Co0.2Mn0.2]O2 / graphite batteries are designed to confirm the rationality of the model. The simulation results show that the highest temperature of the battery surface during discharging at 1 C and 4 C are 42.85 °C and 61.25 °C, and the experimental results are 42.50 °C and 62.85 °C, respectively. The electrode heat generation mainly comes from the reaction heat of cathode and anode during 1 C charge process, the maximum power is 1.2 W and 0.6 W, respectively. In the discharge process, the cathode dominates the reaction contribution of 1.02 W and the reaction heat power from the anode is only 0.016 W. The capacity of heat dissipation can be increased by enhancing the convective heat transfer coefficient and air velocity within a reasonable range. The proposed electrochemical-thermal coupling model is valuable to evaluate the heat behavior and promote the battery development.
SFC‐Based IoT Provisioning on a Hybrid Cloud‐Fog Computing with a Minimized Latency
Authors: Atinafu Dawit Asmero , Tulu Muluneh Mekonnen
Published: August 2024

The increasing heterogeneity of traffic in the Internet of Things (IoT) service demands presents a challenge for computing nodes to meet the computing resources and link bandwidth required. To address this, IoT requests have been virtualized and organized in service function chaining (SFC), which requires a host among hybrid cloud‐fog computing nodes. To find a suitable host for each service function (SF) request, a typical migration algorithm has been used. However, this approach delayed the response due to propagation delays in searching for a valid nearby node. Mission‐critical service demands may not even be served at all. This article addresses this issue by proposing two novel approaches: nearest candidate node selection (NCNS) and fastest candidate node selection (FCNS). These approaches employ software‐defined network (SDN) controllers and the Markovian arrival process, Markovian service process, and single host (M/M/1) queuing model to monitor the maximum possible latency required to meet the SF service demand by each computing node and finally assigning into one with least latency. With the use of these methods, heuristic monitoring of computing resources is made possible, allowing the selection of the most suitable host computing nodes based on proximity or minimal round‐trip time. Moreover, priority‐based fastest candidate node selection (PB‐FCNS), an adaptation of FCNS, accounts for concurrent service requests using the general arrival process, general service process, and single host node (G/G/1) queuing model. Compared to traditional migration algorithms, NCNS and FCNS provide significant improvements in reducing round‐trip time by 5% and decreasing the probability of unsuccessful service function chains by 55%. Despite the cost of installation, employing these methods in conjunction with SDN controllers can reduce latency, maximize service success rates, and guarantee the delivery of heterogeneous service functions.
Brake Drum Temperature Rise and Its Influence on Truck Driving Safety in Tunnel Groups Section
Authors: He Yunyong , He Enhuai , Zhang Le , Gao Jianping , Yang Changfeng , Sun Lu , Yang Haotian , Gong Zhen , Liu Ziqiang
Published: August 2024

High risk of braking easily causes more safety accidents. In this paper, the driving experiments on G350 Gengda‐Yingxiu section containing continuous downhill tunnel group. Three‐axle trucks under standard load and overload conditions were considered. The research proposes a method for ensuring safe truck driving on continuous downhill sections of mountain roads based on the rise in brake drum temperature. The study collects data on brake drum temperature and braking duration from an experimental vehicle under the coupling action of human‐vehicle‐road‐environment. Through comparative analysis, theoretical derivation, and model construction, conclusions are drawn. The results indicate that the rise in brake drum temperature is influenced by the factors such as overload, alignment, road slope, and sections with bright and dark lines. The initial brake drum temperature, operating speed, and total vehicle mass are identified as the main controlling factors for the change in brake drum temperature. The study also demonstrates that water drenching can significantly reduce the rate of brake drum temperature rise, thereby ensuring driving safety. Furthermore, a model is constructed based on the relationship between brake drum temperature rise and various factors, which allows for the calculation of the corresponding safe slope length and average slope gradient. This model can be used for evaluating or designing overall load requirements. The research on brake drum temperature rise characteristics and braking behaviour under drenching conditions provides effective support for route design, traffic management, and the establishment of safety service facilities.
Bonding Durability Evaluation of Polymer‐Modified Emulsified Asphalt Microsurfacing
Authors: Fu Hao , Chen Qian , Sun Xiaolong , Zhang Wenwu , Wang Shanshan
Published: August 2024

At present, there are few research studies on the durability of microsurfacing. To further improve the service quality and durability of microsurfacing, five kinds of polymer‐modified emulsified asphalt were used to prepare microsurfacing mixture. Based on the mixing time, wet track abrasion test, and load wheel test, the composition rationality of the microsurfacing mixture was verified. The influence of different polymer‐modified emulsified asphalt on the water damage resistance, deformation resistance, and skid resistance of the microsurfacing was analyzed. The destructive effects of complex climatic conditions on the microsurfacing were simulated by means of damp heat aging, freeze‐thaw cycle, and xenon lamp light aging treatment. Taking the wear resistance and pull‐off properties after aging treatment and the change rate of various properties before and after treatment as evaluation indexes, the bonding durability of the microsurfacing was comprehensively evaluated by the ideal point method of entropy weight. The results show that the water damage resistance, abrasion resistance, and deformation resistance of the microsurfacing have a high correlation with the mechanical strength and adhesion performance of the modified emulsified asphalt binder. Xenon lamp aging has a significant impact on the bonding performance of the microsurfacing. Waterborne epoxy resin can effectively improve the bonding performance and bonding durability of the microsurfacing. Waterborne polyurethane can improve the freeze‐thaw resistance and xenon lamp aging resistance of the microsurfacing.
Temperature Anomalies in the Northern and Southern Hemispheres: Evidence of Persistence and Trends
Authors: Gil-Alana Luis Alberiko , Carmona-González Nieves
Published: August 2024

This paper analyses temperature anomalies in the northern and southern hemispheres, and the differences between the two in order to estimate the time trend coefficients and the degrees of persistence in the data. Analysing the entire sample period (from 1880m1 to 2022m10), the results indicate lower degrees of persistence and more acute trends in northern hemisphere temperatures. We also observe some degree of persistence and a positive trend for the differenced series. Finally, observing the evolution of these two factors over the last 50 years, we see that in northern temperatures, both the degree of persistence and the time trend have increased over time, whereas similar increases were not observed in southern temperatures.
Figure 5 from Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer
Authors: Cai Xin-Jia , Peng Chao-Ran , Zhang Jian-Yun , Li Xue-Fen , Wang Xu , Han Ying , Zhang He-Yu , Peng Xin , Li Tie-Jun
Published: August 2024

Multiplexed immunofluorescence staining in A, OLK and B, OSCC. C, Ratio of MCTC in OLK was higher than that of MCT, D, whereas the ratio of MCT was greater than that of MCTC in OSCC. E, Ratio of MCT was grouped based on the standardized log-rank statistic, and F, the KM curve survival analyses showed an association between MCT and poor prognosis of OSCC. *, P < 0.05; ***, P < 0.001. DAPI, 4,6-diamidino-2-phenylindole.
The Future of Speech Online: International Cooperation for a Free & Open Internet
Authors: Clegg Nick
Published: August 2024

This essay explores the impact that the resurgence of sovereignty has had on freedom of online speech. I argue that, in the past few decades, the internet has undergone a radical transformation from a universal tool of free communication to one that is increasingly fragmented into national and regional siloes. While acknowledging that recent internet regulation by democratic governments has been both necessary and inevitable, I argue that the authoritarian internet model-with citizens segregated from the rest of the global internet and subject to extensive surveillance and censorship - is on the rise, presenting a real risk to the internet as we know it. In the face of this threat, the world's techno-democracies need to work together to protect the freedoms that the internet has so far made possible.
Free Speech on the Internet: The Crisis of Epistemic Authority
Authors: Leiter Brian
Published: August 2024

Much of our knowledge of the world comes not from direct sensory experience, but from reliance on epistemic authorities: individuals or institutions that tell us what we ought to believe. For example, what most of us believe about natural selection, climate change, or the Holocaust comes from our reliance on epistemic authorities (scientists, historians). Sustaining epistemic authority depends, crucially, on social institutions that inculcate reliable second-order norms about whom to believe about what. The traditional media were crucial, in the age of mass democracy, with promulgating and sustaining such norms. The internet has obliterated the intermediaries who made that possible, and, in the process, undermined the epistemic standing of actual experts. This essay considers some possible changes to existing free speech doctrine to remedy the epistemological crisis brought about by the internet.
The Fate of American Democracy Depends on Free Speech
Authors: Nossel Suzanne
Published: August 2024

The freedom of speech - an essential cornerstone of American democracy - is under direct attack, leaving American institutions, civic culture, and society deeply vulnerable. Restrictions on books and educational curricula, limits on assembly rights, the rampant spread of disinformation, the chill of “cancel culture ” and online abuse- all impinge upon the open exchange of ideas that the First Amendment was intended to underwrite. Encroachments on freedom of expression emanate from all sides of the political spectrum and through both formal and informal channels. It is imperative that efforts to contain and surmount the crisis of American democracy include a sharpened focus on the defense of free speech, an essential counterpart to voting rights, civil rights, and a healthy democratic culture.
The Unfortunate Consequences of a Misguided Free Speech Principle
Authors: Post Robert C.
Published: August 2024

For at least the past half-century, Americans have been committed to a “free speech principle,” holding that speech is to be encouraged because it serves to produce knowledge, to enable the development of personal autonomy, and to facilitate the self-governance of the nation. In this essay, I argue that any such abstract free speech principle is fundamentally misguided. The value of speech is instead the value of the social practice within which speech occurs. Speech is to be encouraged when it advances the purpose of the social practice in which it is embedded. For constitutional purposes, the most important social practice established by communication is the public sphere, whose development in the eighteenth century made possible democratic self-governance. The health of a democracy depends upon whether its public sphere can produce a public opinion capable of legitimating the state. This turns on the quality of a nation's politics, not on the quantity of its speech. Americans who conceptualize the current crisis as requiring rededication to the free speech principle thus essentially misdiagnose the nature of our contemporary emergency. We need to repair our politics, not our speech.
The First Amendment Meets the Virtual Public Square
Authors: Stanger Allison
Published: August 2024

Section 230, the twenty-six words that created the internet, has become the twenty-six words that are breaking the First Amendment. Section 230's blanket liability shield for social media platforms is harming our children and our democracy. In this essay, I narrate the story of what Section 230 enabled-the rise of the virtual public square, a circumstance that the framers could never have imagined-and explore its consequences for human well-being and freedom of expression. I conclude that Section 230 must be repealed to unleash First Amendment jurisprudence to confront the threats to the republic in the age of generative AI, as well as to usher in the next round of internet innovation in service of constitutional democratic sustainability. Bipartisan legislation has been introduced to sunset Section 230 as of December 31,2025. Those who believe in the enduring promise of American constitutional democracy should support its passage.