bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats
Authors: Wei Wei , Liu Aihua , Liu Min , Li Mingfeng , Wu Xinghan , Qin Chuan , Shan Zhongyan , Zhang Ling
Published: July 2024

Background

Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism‐like behavior of IMH offspring.

Methods

The animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid‐stimulating hormone (TSH) were detected using enzyme‐linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open‐field test, three‐chamber sociability test, and Morris water maze, to explore the autistic‐like behavior of 40‐day‐old offspring rats.

Results

The ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly.

Conclusion

The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic‐like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.
Lesions Causing Alice in Wonderland Syndrome Map to a Common Brain Network Linking Body and Size Perception
Authors: Friedrich Maximilian U. , Baughan Elijah C. , Kletenik Isaiah , Younger Ellen , Zhao Charlie W. , Howard Calvin , Ferguson Michael A. , Schaper Frederic L.W.V.J. , Chen Amalie , Zeller Daniel , Piervincenzi Claudia , Tommasin Silvia , Pantano Patrizia , Blanke Olaf , Prasad Sashank , Nielsen Jared A. , Fox Michael D.
Published: July 2024

Objective

Alice in Wonderland syndrome (AIWS) profoundly affects human perception of size and scale, particularly regarding one's own body and the environment. Its neuroanatomical basis has remained elusive, partly because brain lesions causing AIWS can occur in different brain regions. Here, we aimed to determine if brain lesions causing AIWS map to a distributed brain network.

Methods

A retrospective case–control study analyzing 37 cases of lesion‐induced AIWS identified through systematic literature review was conducted. Using resting‐state functional connectome data from 1,000 healthy individuals, the whole‐brain connections of each lesion were estimated and contrasted with those from a control dataset comprising 1,073 lesions associated with 25 other neuropsychiatric syndromes. Additionally, connectivity findings from lesion‐induced AIWS cases were compared with functional neuroimaging results from 5 non‐lesional AIWS cases.

Results

AIWS‐associated lesions were located in various brain regions with minimal overlap (≤33%). However, the majority of lesions (≥85%) demonstrated shared connectivity to the right extrastriate body area, known to be selectively activated by viewing body part images, and the inferior parietal cortex, involved in size and scale judgements. This pattern was uniquely characteristic of AIWS when compared with other neuropsychiatric disorders (family‐wise error‐corrected p < 0.05) and consistent with functional neuroimaging observations in AIWS due to nonlesional causes (median correlation r = 0.56, interquartile range 0.24).

Interpretation

AIWS‐related perceptual distortions map to one common brain network, encompassing regions critical for body representation and size‐scale processing. These findings lend insight into the neuroanatomical localization of higher‐order perceptual functions, and may inform future therapeutic strategies for perceptual disorders. ANN NEUROL 2024;96:662–674
Highly Selective Photocatalytic Synthesis of Acetic Acid at 0–25 °C
Authors: Zong Xupeng , Chu Yi‐Chun , Tang Yu , Li Yuting , Wu Xin‐Ping , Sun Zaicheng , Tao Franklin
Published: July 2024

Acetic acid (AA), a vital compound in chemical production and materials manufacturing, is conventionally synthesized by starting with coal or methane through multiple steps including high‐temperature transformations. Here we present a new synthesis of AA from ethane through photocatalytic selective oxidation of ethane by H2O2 at 0–25 °C. The catalyst designed for this process comprises g‐C3N4 with anchored Pd1 single‐atom sites. In situ studies and computational simulation suggest the immobilized Pd1 atom becomes positively charged under photocatalytic condition. Under photoirradiation, the holes on the Pd1 single‐atom of OH−Pd1
/g‐C3N4 serves as a catalytic site for activating a C−H instead of C−C of C2H6 with a low activation barrier of 0.14 eV, through a concerted mechanism. Remarkably, the selectivity for synthesizing AA reaches 98.7 %, achieved under atmospheric pressure of ethane at 0 °C. By integrating photocatalysis with thermal catalysis, we introduce a highly selective, environmentally friendly, energy‐efficient synthetic route for AA, starting from ethane, presenting a promising alternative for AA synthesis. This integration of photocatalysis in low‐temperature oxidation demonstrates a new route of selective oxidation of light alkanes.
A Cost‐Effective Sulfide Solid Electrolyte Li7P3S7.5O3.5 with Low Density and Excellent Anode Compatibility
Authors: Li Hui , Lin Qiaosong , Wang Jinzhu , Hu Lv , Chen Fang , Zhang Zhihua , Ma Cheng
Published: July 2024

The commercialization of all‐solid‐state Li batteries (ASSLBs) demands solid electrolytes with strong cost‐competitiveness, low density (for enabling satisfactory energy densities), and decent anode compatibility (the need for cathode compatibility can be circumvented by the cathode coating techniques that are widely applied in sulfide‐based ASSLBs). However, none of the reported oxide, sulfide, or chloride solid electrolytes meets these requirements simultaneously. Here, we design a Li7P3S7.5O3.5 (LPSO) solid electrolyte, which shows a combination of all the aforementioned characteristics. The synthesis of this material does not need the expensive Li2S, so the raw materials cost is only $14.42/kg, which, unlike most solid electrolytes, lies below the $50/kg threshold for commercialization. The density of LPSO is 1.70 g cm−3, considerably lower than those of the oxide (typically above 5 g cm−3) and chloride (around 2.5 g cm−3) solid electrolytes. Besides, LPSO also shows excellent anode compatibility. The Li|LPSO|Li cell cycles stably with a potential of ~50 mV under 0.1 mA cm−2 for over 4200 h at 25 °C, and the all‐solid‐state pouch cell with the Si anode shows a capacity retention of 89.29 % after 200 cycles under 88.6 mA g−1 at 60 °C.
Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells
Authors: Cosottini Lucrezia , Geri Andrea , Ghini Veronica , Mannelli Michele , Zineddu Stefano , Di Paco Giorgio , Giachetti Andrea , Massai Lara , Severi Mirko , Gamberi Tania , Rosato Antonio , Turano Paola , Messori Luigi
Published: July 2024

Aurothiomalate (AuTM) is an FDA‐approved antiarthritic gold drug with unique anticancer properties. To enhance its anticancer activity, we prepared a bioconjugate with human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of apoferritin with excess AuTM yielded a single adduct, that was characterized by ESI MS and ICP‐OES analysis, using three mutant ferritins and trypsinization experiments. The adduct contains ~3 gold atoms per ferritin subunit, arranged in a small cluster bound to Cys90 and Cys102. MD simulations provided a plausible structural model for the cluster. The adduct was evaluated for its pharmacological properties and was found to be significantly more cytotoxic than free AuTM against A2780 cancer cells mainly due to higher gold uptake. NMR‐metabolomics showed that AuTM bound to HuHf and free AuTM induced qualitatively similar changes in treated cancer cells, indicating that the effects on cell metabolism are approximately the same, in agreement with independent biochemical experiments. In conclusion, we have demonstrated here that a molecularly precise bioconjugate formed between AuTM and HuHf exhibits anticancer properties far superior to the free drug, while retaining its key mechanistic features. Evidence is provided that human ferritin can serve as an excellent carrier for this metallodrug.
Tris(triazolo)triazine‐Based Covalent Organic Frameworks for Efficiently Photocatalytic Hydrogen Peroxide Production
Authors: Zhang Zhenwei , Zhang Qi , Hou Yuxin , Li Jiali , Zhu Shanshan , Xia Hong , Yue Huijuan , Liu Xiaoming
Published: July 2024

Two‐dimensional covalent organic frameworks (2D‐COFs) have recently emerged as fascinating scaffolds for solar‐to‐chemical energy conversion because of their customizable structures and functionalities. Herein, two tris(triazolo)triazine‐based COF materials (namely COF‐JLU51 and COF‐JLU52) featuring large surface area, high crystallinity, excellent stability and photoelectric properties were designed and constructed for the first time. Remarkably, COF‐JLU51 gave an outstanding H2O2 production rate of over 4200 μmol g−1 h−1 with excellent reusability in pure water and O2 under one standard sun light, that higher than its isomorphic COF‐JLU52 and most of the reported metal‐free materials, owing to its superior generation, separation and transport of photogenerated carriers. Experimental and theoretical researches prove that the photocatalytic process undergoes a combination of indirect 2e− O2 reduction reaction (ORR) and 4e− H2O oxidation reaction (WOR). Specifically, an ultrahigh yield of 7624.7 μmol g−1 h−1 with apparent quantum yield of 18.2 % for COF‐JLU52 was achieved in a 1 : 1 ratio of benzyl alcohol and water system. This finding contributes novel, nitrogen‐rich and high‐quality tris(triazolo)triazine‐based COF materials, and also designate their bright future in photocatalytic solar transformations.
Stereodivergent Total Synthesis of Tacaman Alkaloids
Authors: Chen Xiangtao , Wang Huijing , Zeng Jie , Li Qiuhong , Zhang Tonghui , Yang Qiaoyun , Tang Pei , Chen Fen‐Er
Published: July 2024

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer–Villiger oxidation of cyclohexanone, which was developed to produce seven‐membered lactones and establish the required stereochemistry at the C14 position (92 % yield, 99 % ee, 500 mg scale). Cis‐ and trans‐tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid‐triggered, tunable acyl‐Pictet–Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl‐Pictet–Spengler cyclization cascade. By strategically using these two reactions and the late‐stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.
A Functional Switch Between Asperfumene and Fusicoccadiene Synthase and Entrance to Asperfumene Biosynthesis through a Vicinal Deprotonation‐Reprotonation Process
Authors: Liu Jing‐Yuan , Lin Fu‐Long , Taizoumbe Kizerbo A. , Lv Jian‐Ming , Wang Yong‐Heng , Wang Gao‐Qian , Chen Guo‐Dong , Yao Xin‐Sheng , Hu Dan , Gao Hao , Dickschat Jeroen S.
Published: July 2024

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and—according to a structural model—active site architecture are highly similar to those of the fusicocca‐2,10(14)‐diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6–5–5–5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation‐reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residue F65 is substituted by I65 in AfAS. Intriguingly, site‐directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes.
Enhancing Effect of Fullerene Guest and Counterion on the Structural Stability and Electrical Conductivity of Octahedral Metallo‐Supramolecular Cages
Authors: Lu Shuai , Zhang Ziang , Zhu Yiying , Tao Ye , Lin Quanjie , Zhang Qian , Lv Xin , Hua Lei , Chen Zhi , Wang Heng , Zhuang Gui‐Lin , Zhang Qian‐Chong , Guo Cunlan , Li Xiaopeng , Yu Xiujun
Published: July 2024

Metallo‐supramolecular cages have garnered tremendous attention for their diverse yet molecular‐level precision structures. However, the physical properties of these supramolecular ensembles, which are of potential significance in molecular electronics, remain largely unexplored. We herein constructed a series of octahedral metallo‐cages and cage‐fullerene complexes with notably enhanced structural stability. As such, we could systematically evaluate the electrical conductivity of these ensembles at both the single‐molecule level and aggregated bulk state (as well‐defined films). Our findings reveal that counteranions and fullerene guests play a pivotal role in determining the electrical conductivity of the aggregated state, while such effects are less significant for single‐molecule conductance. Both the counteranions and fullerenes effectively tune the electronic structures and packing density of metallo‐supramolecular assemblies, and facilitate efficient charge transfer between the cage hosts and fullerenes, resulting in a notable one order of magnitude increase in the electrical conductivity of the aggregated state.
Coordination Engineering of Fe‐Centered Catalysts for Superior Li−S Battery Performance
Authors: Yuan Hao , Yang Jing , Zhang Yong‐Wei
Published: July 2024

Iron‐nitrogen functionalized graphene has emerged as a promising cathode host for rechargeable lithium‐sulfur batteries (RLSBs) due to its affordability and enhanced battery performance. To optimize its catalytical efficiency, we propose a novel approach involving coordination engineering. Our investigation spans a plethora of catalysts with varied coordination environments, focusing on elements B, C, N and O. We revealed that Fe−C4 and Fe−B2C2−h are particularly effective for promoting Li2S oxidation, whereas Fe‐N4 excels in catalyzing the sulfur reduction reaction (SRR). Importantly, our study identified specific descriptors – namely, the Integrated Crystal Orbital Hamilton Population (ICOHP) and the bond length between Fe and S in Li2S adsorbed state – as the most effective predictive descriptors for Li2S oxidation barriers. Meanwhile, Li2S adsorption energy emerges as a reliable descriptor for assessing the SRR barrier. These identified descriptors are expected to be instrumental in rapidly identifying promising cathode hosts across various metal‐centered systems with diverse coordination environments. Our findings not only offer valuable insights into the role of coordination environment, but also present an effective path for rapidly identifying high performance catalysts for RLSBs, enabling the acceleration of advanced RLSBs development.
Enzymatic Functionalization of RNA Oligonucleotides by Terminal Uridylyl Transferase Using Fluorescent and Clickable Nucleotide Analogs
Authors: Dutta Swagata , Srivatsan Seergazhi G.
Published: July 2024

We report a systematic study on controlling the enzyme activity of a terminal uridylyl transferase (TUTase) called SpCID1, which provides methods to effect site‐specific incorporation of a single modified nucleotide analog at the 3′‐end of an RNA oligonucleotide (ON). Responsive heterocycle‐modified fluorescent UTP probes that are useful in analyzing non‐canonical nucleic acid structures and azide‐ and alkyne‐modified UTP analogs that are compatible for chemoenzymatic functionalization were used as study systems. In the first strategy, we balanced the concentration of essential metal ion cofactors (Mg2+ and Mn2+ ions) to restrict the processivity of the enzyme, which gave a very good control on the incorporation of clickable nucleotide analogs. In the second approach, borate that complexes with 2′ and 3′ oxygen atoms of a ribose sugar was used as a reversibly binding chelator to block repeated addition of nucleotide analogs. Notably, in the presence of heterocycle‐modified fluorescent UTPs, we obtained single‐nucleotide incorporated RNA products in reasonable yields, while with clickable nucleotides yields were very good. Further, 3′‐end azide‐ and alkyne‐labeled RNA ONs were post‐enzymatically functionalized by CuAAC and SPAAC reactions with fluorescent probes. These strategies broaden the scope of TUTase in site‐specifically installing modifications of different types onto RNA for various applications.
Enzyme‐Powered, Label‐Free DNA Walker for Uracil‐DNA Glycosylase Detection at Single‐Cell Level
Authors: Li Wei , Wang Shuaijing , Zong Haotian , Li Jiayue , Zhou Yi , Wang Zhenguang
Published: July 2024

Uracil‐DNA glycosylase (UDG) plays a crucial role in the removal of damaged uracil bases, thereby upholding genetic stability and integrity. An enzyme‐powered, label‐free DNA walker was devised for UDG activity detection. Initially, a label‐free DNA track, incorporating a gold nanoparticle (AuNP), multiple hairpin structures, and various swing arms, was engineered for walking mechanism. The hairpin structure was meticulously crafted to include a G‐quadruplex sequence, enabling the generation of a label‐free fluorescence signal. The swing arm remained inert in the absence of UDG, but became activated upon the introduction of UDG, thereby initiating the enzyme‐powered walking process and generating significant dissociative G‐quadruplex sequences. By integrating a selective fluorescent dye into the design, an enhanced label‐free fluorescence response was achieved. The proposed DNA walker presented a direct and label‐free approach for UDG detection, demonstrating exceptional sensitivity with a detection limit of 0.00004 U/mL. Using the uracil glycosylase inhibitor (UGI) as an inhibitory model, inhibitor assay was conducted with satisfactory precision. Furthermore, successful analysis of cellular UDG at the single‐cell level was accomplished. Consequently, the developed DNA walker serves as a label‐free, selective, and sensitive tool for UDG activity assessment, showing great potential for applications in disease diagnosis, inhibitor screening, and biomedical investigations.
Synthesis, Antimicrobial, Molecular Docking Against Bacterial and Fungal Proteins and In Silico Studies of Glucopyranoside Derivatives as Potent Antimicrobial Agents
Authors: Islam Mazherul , Hossain Ahad , Yamari Imane , Abchir Oussama , Chtita Samir , Ali Ferdausi , Kawsar Sarkar M. A.
Published: July 2024

Carbohydrate derivatives play a crucial roles in biochemical and medicinal research, especially in the fields of chemistry and biochemistry. From this perspective, the present study was designed to explore the synthesis of methyl α‐D‐glucopyranoside derivatives (1–8), focusing on their efficacy against bacterial and fungal inhibition. The structure of the synthesized compounds was ascertained using FTIR, 1H‐NMR, 13C‐NMR, mass and elemental analyses. Antimicrobial screening revealed strong antifungal properties, with compound 7 exhibiting minimum inhibitory concentrations (MICs) ranging from 16–32 μg/L and minimum bactericidal concentrations (MBCs) ranging from 64–128 μg/L. Incorporating decanoyl acyl groups at C‐2 and C‐3 of (7) significantly improved the efficacy against bacteria and fungi. Structure‐activity relationship (SAR) analysis indicated that adding nonanoyl and decanoyl groups to the ribose moiety enhanced potency against both bacterial and fungal strains. Computational methods, including molecular docking, density functional theory (DFT), Petra, Osiris, Molinspiration (POM) evaluation, and molecular dynamics (MD) simulations, were used to assess the efficacy of these derivatives. Compounds 6 and 7, which presented nonanoyl and decanoyl substituents, demonstrated greater efficacy. In addition, DFT studies identified compound 8 as possessing ideal electronic properties. Molecular docking revealed that compound 8 exhibits exceptional binding affinities to bacterial proteins, conferring potent antibacterial and antifungal activities. In addition, pharmacokinetic optimization via POM analysis highlighted compounds 1 and 2 as promising bioavailable drugs with minimal toxicity. Molecular dynamics simulations confirmed the stability of the 2‐S. aureus complex, revealing the therapeutic potential of compounds 2 and 8. Future experiments are required to validate their efficacy for pharmaceutical development. The integration of in vitro and in silico methods, including DFT anchoring dynamics and molecular dynamics simulations, provides a solid framework for the advancement of effective anti‐infective drugs.
Management of extensive portal vein thrombosis via thrombolysis and thrombectomy without underlying liver disease: A case report
Authors: Gul Mohammadshah Isam , Umer Waseem , Nawaz Ahmed Daniyal , Elhissi Mohammad J. H. , Zahid Muhammad
Published: July 2024

Key Clinical Message

Portal vein thrombosis (PVT) is a rare condition, particularly in non‐cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.
Multiple intracranial tuberculomas in an elderly patient: A central nervous system tuberculosis case in the emergency department
Authors: Farrokhnia Mehrdad , Mirkamali Hanieh , Alizadeh Seyed Danial , Rezaei Zadeh Rukerd Mohammad
Published: July 2024

Key Clinical Message

A 67‐year‐old male presented to the emergency department with a 7‐day history of fever, malaise, myalgia, headache, and a seizure episode. Physical examination showed stable vital signs but a fever. Laboratory tests indicated leukocytosis, anemia, thrombocytosis, and elevated inflammatory markers. Imaging revealed multiple intracranial lesions, and cerebrospinal fluid analysis confirmed the presence of acid‐fast bacilli. The patient responded well to anti‐tuberculosis therapy, showing significant clinical improvement within 8 weeks.
Achieving Non‐Interfacial Blocking Zinc Ion Transport Based on MOF Derived Manganese Oxides and Amorphous Carbon Hybrid Materials
Authors: Jiang Siyu , Han Wenjuan , Fang Luan , Zhang Shu , Xue Xiangxin , Nie Ping , Liu Bo , Zhao Cuimei , Lu Ming , Chang Limin
Published: July 2024

How to coordinate electron and ion transport behavior across scales and interfaces within ion battery electrodes? The exponential increase in surface area observed in nanoscale electrode materials results in an incomprehensibly vast spatial interval. Herein, to address the problems of volume expansion, dissolution of cathode material, and the charge accumulation problem existing in manganiferous materials for zinc ion batteries, metal organic framework is utilized to form the architecture of non‐interfacial blocking ~10 nm Mn2O3 nanoparticles and amorphous carbon hybrid electrode materials, demonstrating a high specific capacity of 361 mAh g−1 (0.1 A g−1), and excellent cycle stability of 105 mAh g−1 after 2000 cycles under 1 A g−1. The uniform and non‐separated disposition of Mn and C atoms constitutes an interconnected network with high electronic and ionic conductivity, minimizing issues like structural collapse and volume expansion of the electrode material during cycling. The cooperative insert mechanism of H+ and Zn2+ are analyzed via ex‐situ XRD and in‐situ Raman tests. The model battery is assembled to present practical possibilities. The results indicate that MOF‐derived carbonization provides an effective strategy for exploring Mn‐based electrode materials with high ion and electron transport capacity.
Photothermal Effect and Fenton‐Like Oxidation for Synergistic Removal of Fluoroquinolones Antibiotics under Near‐Neutral Conditions
Authors: Jiao Lanya , Meng Jiao , Wang Shujun , Sun Xuan
Published: July 2024

Defect‐enriched mesoporous CuO nanosheets (NSs) were constructed to investigate the cooperative photo‐Fenton and photothermal‐Fenton catalysis on degradation of fluoroquinolones (FQ) antibiotics. The oxygen vacancies provide abundant active sites to bind the substrates and inhibit charge recombination, by all means to enhance Fenton‐like activity. Two disparate spectral selective functions of photoexcitation and photothermal conversion were achieved on CuO NS, which to promote the Fenton activity synergistically. Visible light induced photoexcitation to facilitate the generation of Cu+ and ⋅OH, while near‐infrared light converted into heat to promote charge separation and accelerate medium transport. Ultimately, as a unitary catalyst system, the CuO NS integrated the Lewis acid catalysis, Fenton‐like catalysis and photothermal catalysis that rapidly and sustainably degraded antibiotics under near‐neutral conditions.
Isolation and characterization of synthesis intermediates and side products in hexahydrocannabiphorol
Authors: Schirmer Willi , Gjuroski Ilche , Vermathen Martina , Furrer Julien , Schürch Stefan , Weinmann Wolfgang
Published: July 2024

After the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market. Various vendors in online shops claim that HHCP is made from CBD, even though they possess different alkyl chain lengths. An HHCP sample was analyzed by gas chromatography coupled to mass spectrometry (GC‐MS), showing that a mixture of molecules with the same or a similar molecular mass as HHCP was present. Six different substances could be isolated from this sample using column chromatography. Four phenols ((9R)‐HHCP, iso‐HHCP, cis‐HHCP, and abn‐HHCP) and two ketones (possible intermediates to (9R)‐HHCP and abn‐HHCP) were identified by various nuclear magnetic resonance spectroscopy (NMR) techniques. (9S)‐HHCP was obtained in an impure fraction. In addition, a fraction was obtained that showed characteristic molecular and fragment ions consistent with bisalkylated products from the synthesis of similar compounds. The presence of abnormal cannabinoids (abn‐HHCP) and bisalkylated cannabinoids is a confirmation that this sample was produced purely synthetically as initially suspected, as these compounds have not been reported in Cannabis. Chiral derivatization of the phenols with Mosher acid chlorides showed that only iso‐HHCP was present as a scalemic mixture, indicating a good stereocontrol of this synthetic procedure.
The analysis of methylamphetamine and para‐hydroxy‐methylamphetamine in post‐mortem hair samples using liquid chromatography–tandem mass spectrometry
Authors: Mantinieks Dylan , Drummer Olaf H. , Schumann Jennifer , Gerostamoulos Dimitri
Published: July 2024

External contamination is a well‐recognized limitation of hair analysis for drugs of abuse like methylamphetamine (MA), and there are no guidelines regarding the analysis of specific metabolites of MA to assist interpretation. We developed an analytical method to detect MA, amphetamine (AMP), and para‐hydroxy‐methylamphetamine (p‐OH‐MA) in hair and present their concentrations among a cohort of deceased persons positive for MA in blood (n = 63). Hair samples (≤ 3 cm) were washed with dichloromethane and water prior to extraction using a methanolic micro‐pulverization. The reconstituted hair extracts were separated on a UCT Selectra® Aqueous C18 HPLC Column (100 × 2.1 mm, 3 μm) by gradient elution and detected using a Sciex Triple Quad 6500+ system. Validation was satisfactory, and the lower limits of quantitation were 0.01 ng/mg for MA and AMP and 0.001 ng/mg for p‐OH‐MA. The median hair concentrations of MA, AMP, and p‐OH‐MA were 13 ng/mg (range = 0.015–49; n = 51), 1.1 ng/mg (range = 0.018–44; n = 60), and 0.020 ng/mg (range = 0.0012–0.38, n = 62), respectively. These concentrations in hair were strongly positively correlated (r = .7202 to .8641, p < .001), suggesting similar modes of incorporation. Moreover, the wash/hair ratios were indicative of external contamination, especially among the soiled group of hair samples. Therefore, further studies are necessary to determine concentrations of p‐OH‐MA in living MA users and confirm if this metabolite constitutes a potential marker of MA consumption.
Growth–defense trade‐offs promote habitat isolation between recently‐diverged species
Authors: Harenčár Julia G. , Salazar‐Amoretti Diego , García‐Robledo Carlos , Kay Kathleen M.
Published: July 2024

Trade‐offs are crucial for species divergence and reproductive isolation. Trade‐offs between investment in growth versus defense against herbivores are implicated in tropical forest diversity. Empirically exploring the role of growth–defense trade‐offs in closely related species' reproductive isolation can clarify the eco‐evolutionary dynamics through which growth–defense trade‐offs contribute to diversity. Costus villosissimus and C. allenii are recently diverged, interfertile, and partially sympatric neotropical understory plant species primarily isolated by divergent habitat adaptation. This divergent adaptation involves differences in growth rate, which may constrain investment in defense. Here, we investigate growth–defense trade‐offs and how they relate to the divergent habitat adaptation that isolates these species. We characterize leaf toughness and chemistry, evaluate the feeding preferences of primary beetle herbivores in controlled trials and field‐based experiments, and investigate natural herbivory patterns. We find clear trade‐offs between growth and defense: slower‐growing C. allenii has tougher leaves and higher defensive chemical concentrations than faster‐growing C. villosissimus. Costus villosissimus has rapid growth‐based drought avoidance, enabling growth in drier habitats with few specialist herbivores. Therefore, growth–defense trade‐offs mediate synergistic biotic and abiotic selection, causing the divergent habitat adaptation that prevents most interspecific mating between C. villosissimus and C. allenii. Our findings advance understanding of ecological speciation by highlighting the interplay of biotic and abiotic selection that dictates the outcome of trade‐offs.
Assessing the performance of short 18S rDNA markers for environmental DNA metabarcoding of marine protists
Authors: Zimmermann Heike H. , Harðardóttir Sara , Ribeiro Sofia
Published: July 2024

Marine protists are globally distributed and sensitive to environmental conditions, which makes them a focal group when studying the effects of climate change on biodiversity and ocean health. However, they are a highly diverse group with varying evolutionary histories and morphologies and widely variable preservation potential in the fossil record. Thus, their past diversity and composition are poorly known. Paleogenetics, which relies, among other approaches, on DNA metabarcoding of sedimentary ancient DNA (sedaDNA), provides a promising avenue to explore the past history and responses of marine protists to global change. Choosing the right marker for sedaDNA studies is critical, striking a balance between marker length and taxonomic resolution. While marker guides exist for modern environmental DNA surveys, a thorough assessment of existing short markers for sedaDNA studies targeting protists is lacking. In this study, we report on a comparison of in silico PCR for eight short 18S rDNA markers, including one from the Tara Oceans initiative and a longer marker commonly used in modern marine eDNA studies. We analyze their taxonomic coverage and resolution, taxonomic overlap and uniqueness between markers, co‐amplification of non‐protist taxa, and amplicon size differences across taxonomic groups. Additionally, we provide a detailed analysis of diatoms, dinoflagellates, haptophytes, and chlorophytes. Our study is aimed at supporting project‐specific marker choices for characterizing protist composition and diversity. While we focus on marine protists, our results are applicable to other aquatic and terrestrial environments.
Potentiometric determination of nitrazepam in pharmaceutical dosage form and spiked plasma using a novel modified carbon paste electrode
Authors: Azab Marwa M. , Rizk Mohamed , Mohamed Omaima M. , Farag Amir Shaaban
Published: July 2024

A newly prepared solid contact ion selective electrode based on polyvinyl chloride membrane has been optimized and developed for determining nitrazepam in its pure form and synthetically prepared tablet dosage form. The proposed electrode was fabricated based on zeolite modified carbon paste electrode as a solid contact acting as a support for the membrane of PVC containing the ion complex of nitrazepam‐tetraphenyl borate as an electroactive material, and the plasticizer dibutyl phthalate. By improving the composition, the potentiometric properties were further enhanced, and the sensor achieved a Nernstian slope of 60.89 mV dec−1. The sensor was effective for detecting nitrazepam in the concentration range of 1.0×10−7 to 1.0×10−2 M, with a detection limit of 4.7×10−8 M. The sensor demonstrated excellent reversibility and reproducibility with a fast response time and application over a wide pH range. The developed electrode showed no significant effect when tested with various interfering species. It is successfully applied for accurate determination of nitrazepam in pure form, synthetically prepared tablet and spiked human plasma. The developed technique was validated and demonstrated high accuracy and precision. When compared statistically with the official method, there were no significant differences observed.
Integrity of neural extracellular matrix is required for microglia‐mediated synaptic remodeling
Authors: Cangalaya Carla , Sun Weilun , Stoyanov Stoyan , Dunay Ildiko Rita , Dityatev Alexander
Published: July 2024

Microglia continuously remodel synapses, which are embedded in the extracellular matrix (ECM). However, the mechanisms, which govern this process remain elusive. To investigate the influence of the neural ECM in synaptic remodeling by microglia, we disrupted ECM integrity by injection of chondroitinase ABC (ChABC) into the retrosplenial cortex of healthy adult mice. Using in vivo two‐photon microscopy we found that ChABC treatment increased microglial branching complexity and ECM phagocytic capacity and decreased spine elimination rate under basal conditions. Moreover, ECM attenuation largely prevented synaptic remodeling following synaptic stress induced by photodamage of single synaptic elements. These changes were associated with less stable and smaller microglial contacts at the synaptic damage sites, diminished deposition of calreticulin and complement proteins C1q and C3 at synapses and impaired expression of microglial CR3 receptor. Thus, our findings provide novel insights into the function of the neural ECM in deposition of complement proteins and synaptic remodeling by microglia.
Explaining the decline of China's labor share: A wide replication of Oberfield and Raval (2021)
Authors: Yang Hong , Zhang Wen
Published: July 2024

China's labor share has declined since late 1990s. Using the methodology developed by Oberfield and Raval, this paper estimates China's aggregate capital‐labor elasticity of substitution, leveraging the estimated micro‐level elasticities. The findings indicate that China's aggregate capital‐labor elasticity falls within the range of 0.9 to 1. Utilizing this estimated aggregate elasticity for labor share decomposition, we find that the bias of technical change emerges as the predominant factor driving the decline in labor share.
Magnetically separable spent coffee grounds as a potential novel support for the covalent immobilization of β‐glucosidase for cellobiose hydrolysis
Authors: Bhardwaj Shaifali , Mishra Ankit , Ghosh Debashish , Sinha Anil Kumar
Published: July 2024

BACKGROUND

The industrial‐scale application of enzymes faces obstacles due to elevated costs and difficulties in stability and reuse. In this study, magnetic spent coffee grounds, an ecotoxic waste, have been utilized successfully for the first time to immobilize β‐glucosidase to overcome these challenges.

RESULTS

The spent coffee grounds were magnetized and amine‐functionalized, followed by characterization using various techniques. Under optimized conditions, forming an imine bond between the functionalized support and β‐glucosidase resulted in a 62% immobilization yield (92.81 mg g−1 enzyme loading) and 12.5 U mg−1 activity after immobilization. A relatively small kinetic change was observed in the Km value (902 to 946 μmol L−1) after immobilization, suggesting minimal hindrance by AMSCG3 on substrate access or product release. Moreover, Glu@AMSCG3 showed exceptional stability (>90% residual activity) within a pH range of 3 to 6 after 2 h of incubation at 25 °C. A residual activity of 87.94% was maintained even at 80 °C and pH 5 after 2 h of incubation compared to the free β‐glucosidase, which showed only 6.5% residual activity at the same temperature. When cellobiose was hydrolyzed using Glu@AMSCG3 under optimum conditions, 91.33% cellobiose conversion was achieved initially, and over 79% conversion was maintained for 10 reusability cycles.

CONCLUSION

The improved stability of β‐glucosidase after covalent immobilization on amine‐modified magnetically separable spent coffee grounds indicates their potential as a support matrix for application in enzyme immobilization. © 2024 Society of Chemical Industry (SCI).
Applications of MRI in Schizophrenia: Current Progress in Establishing Clinical Utility
Authors: Sun Hui , Liu Naici , Qiu Changjian , Tao Bo , Yang Chengmin , Tang Biqiu , Li Hongwei , Zhan Kongcai , Cai Chunxian , Zhang Wenjing , Lui Su
Published: July 2024

Schizophrenia is a severe mental illness that significantly impacts the lives of affected individuals and with increasing mortality rates. Early detection and intervention are crucial for improving outcomes but the lack of validated biomarkers poses great challenges in such efforts. The use of magnetic resonance imaging (MRI) in schizophrenia enables the investigation of the disorder's etiological and neuropathological substrates in vivo. After decades of research, promising findings of MRI have been shown to aid in screening high‐risk individuals and predicting illness onset, and predicting symptoms and treatment outcomes of schizophrenia. The integration of machine learning and deep learning techniques makes it possible to develop intelligent diagnostic and prognostic tools with extracted or selected imaging features. In this review, we aimed to provide an overview of current progress and prospects in establishing clinical utility of MRI in schizophrenia. We first provided an overview of MRI findings of brain abnormalities that might underpin the symptoms or treatment response process in schizophrenia patients. Then, we summarized the ongoing efforts in the computer‐aided utility of MRI in schizophrenia and discussed the gap between MRI research findings and real‐world applications. Finally, promising pathways to promote clinical translation were provided.

Evidence Level

2

Technical Efficacy

Stage 3
Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients
Authors: Külekci Büsra , Mollik Madlen , Schwarz Stefan , Perkmann‐Nagele Nicole , Geleff Silvana , Jaksch Peter , Hoetzenecker Konrad , Lambers Christopher , Puchhammer‐Stöckl Elisabeth , Goerzer Irene
Published: July 2024

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post‐transplantation (post‐Tx) strain population is unknown. Here, we deciphered the D and R origin of the post‐Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin‐fixed paraffin‐embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/− alveolar macrophages. In three LTRs, we demonstrate both rapid
D‐strain dissemination and persistence in the transplanted lung for >1 year post‐Tx. Broad inter‐host diversity contrasts with intra‐host genotype sequence stability upon transmission, during follow‐up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long‐term in subsequent episodes of infection, indicating replication of both sources despite pre‐existing immunity.
State of the Science: Evidence‐based treatments for posttraumatic stress disorder delivered via telehealth
Authors: Bruce Madeline J. , Pagán Antonio F. , Acierno Ron
Published: July 2024

Psychotherapy delivered via telehealth technology is not an artifact of the COVID‐19 pandemic. Indeed, widespread, telehealth‐delivered, evidence‐based psychotherapy preceded the pandemic, as did randomized controlled noninferiority trials supporting this modality. It is, thus, not difficult to predict that telehealth will be an integral part of daily clinical life moving forward. With respect to posttraumatic stress disorder (PTSD) specifically, there is a substantial number of studies on the feasibility, acceptability, and effectiveness of evidence‐based treatments provided via videoconferencing. In this review, we delineate the literature establishing strong support for remote delivery of prolonged exposure (PE) and cognitive processing therapy (CPT); there is also promising support for written exposure therapy (WET) and trauma‐focused cognitive behavioral therapy (TF‐CBT). We also mention adjunctive and integrative modifications to better serve patients with PTSD. One such intervention, behavioral activation and therapeutic exposure (BATE), has several studies supporting telehealth delivery, whereas concurrent treatment of PTSD and substance use disorders using the PE protocol (COPE) and cognitive behavioral therapy for insomnia (CBT‐I) would benefit from further research. Integrating instrumental peer support into telehealth‐delivered PE shows promise in retaining patients in treatment. Finally, we provide ideas to maximize telehealth delivery effectiveness, explore future research directions, and discuss ways to advocate for the expansion of telehealth services from an equity perspective.
Vocal Cord Function Return After Larynx Preservation is Associated With Recurrence‐Free Probability
Authors: Adilbay Dauren , Asarkar Ameya A. , Kandula Rema Anisha , Moore‐Medline Tara , Nathan Cherie‐Ann
Published: July 2024

Objectives

Vocal cord fixation is one of the main upstaging features of laryngeal cancer. In our previously conducted retrospective study, vocal cord (VC) mobility restoration after chemoradiotherapy was a favorable prognostic variable. In this prospective study, we examined the significance of VC mobility restoration after definitive treatment as a prognostic variable.

Methods

In this prospective cohort study, we enrolled 30 patients with squamous cell carcinoma of the larynx with VC impairment/fixation (T2/3, T4a) who underwent definitive chemoradiotherapy with complete response. Video laryngoscopy before and at 3 months after treatment was used to evaluate VC mobility. The primary endpoint of the study was the local recurrence‐free probability. Secondary endpoints included recurrence‐free probability, disease‐specific survival (DSS), and overall survival (OS).

Results

The median age of patients was 62 years (IQR 54–67). The primary subsites were the glottis (n = 13) and supraglottis (n = 14). After treatment, 18 (60%) patients had a full recovery of VC mobility, and 12 (40%) patients' VCs were fixed or impaired. Five‐year local recurrence‐free probability was worse in the VC‐impaired group compared to a group with restored VC mobility (46% vs. 85%, p = 0.012). Recurrence‐free probability, OS, and DSS differences were not statistically significant in both groups. VC mobility restoration predicted local recurrence‐free probability on univariable analysis (HR 6.15, 95% CI 1.23–30.6).

Conclusion

In this prospective study, we show that the absence of VC mobility restoration is associated with worse local recurrence‐free probability after definitive laryngeal preservation treatment. Patients with persistent vocal cord immobility warrant closer follow‐up to detect recurrence early.

Level of Evidence

3 Laryngoscope, 135:671–676, 2025
Regularity for a class of integral functionals
Authors: Shuoyang Li , Meng Gao , Hongya Gao
Published: July 2024

This paper deals with regularity properties for variational integrals with the splitting structure of the form
where , is the adjugate matrix of order , and , , , are Carathéodory functions satisfying suitable structural conditions. Local integrability, local boundedness, and local Hölder continuity for local minimizers are derived.
Single‐peak solution for a fractional slightly subcritical problem with non‐power nonlinearity
Authors: Deng Shengbing , Yu Fang
Published: July 2024

We consider the following fractional problem involving slightly subcritical non‐power nonlinearity,
where is a smooth bounded domain in , , , is the fractional critical Sobolev exponent and is a small parameter, is the spectral fractional Laplacian operator. We construct a positive bubbling solution, which concentrates at a nondegenerate critical point of the Robin function by Lyapunov–Schmidt reduction procedure.
TAC report on state psychiatric hospital beds features consumers' voices
Authors: Canady Valerie A.
Published: July 2024

People seeking hospital‐level care for their mental health find it challenging to access a state hospital bed until they have been charged or convicted of a crime, suggests one of the key findings in a new report released by the Treatment Advocacy Center (TAC) and based on the personal stories of family members and an individual with lived experience in the state hospital system.
Legal settlement would expedite MH treatment for Oklahoma detainees
Authors: Enos Gary
Published: July 2024

Yearlong negotiations have led to the proposed settlement of a federal lawsuit over long delays in providing mental health treatment to Oklahoma jail detainees who are found incompetent to stand trial. However, opposition from Gov. Kevin Stitt could derail the remediation plan set out in the settlement, which also requires state legislative approval.