Optimal scaling of protein-water interactions coupled with targeted torsional refinements yields balanced force fields suitable for simulations of single-chain folded proteins, disordered polypeptides, and protein-protein complexes.

All-atom molecular dynamics (MD) simulations based on physics-based force fields, serve as an essential complement to experiments for investigating protein structure, dynamics, and interactions. Despite significant advances in force field development, achieving a consistent balance of molecular interactions that stabilize folded proteins and protein-protein complexes while simultaneously capturing the conformational dynamics of intrinsically disordered polypeptides (IDPs), remains challenging. In this work, we systematically evaluated two current state-of-the-art force fields (i) AMBER ff03ws, and (ii) AMBER ff99SBws, by comprehensively assessing their performance on both folded domains and IDPs.

Modulating neuroplasticity for chronic pain relief: noninvasive neuromodulation as a promising approach.

Chronic neuropathic pain is a debilitating neuroplastic disorder that notably impacts the quality of life of millions of people worldwide. This complex condition, encompassing various manifestations, such as sciatica, diabetic neuropathy and postherpetic neuralgia, arises from nerve damage or malfunctions in pain processing pathways and involves various biological, physiological and psychological processes. Maladaptive neuroplasticity, known as central sensitization, plays a critical role in the persistence of chronic neuropathic pain.

Acetylation-Dependent Compaction of the Histone H4 Tail Ensemble.

Acetylation of the histone H4 tail (H4Kac) has been established as a significant regulator of chromatin architecture and accessibility; however, the molecular mechanisms that underlie these observations remain elusive. Here, we characterize the ensemble features of the histone H4 tail and determine how they change following acetylation on specific sets of lysine residues. Our comprehensive account is enabled by a robust combination of experimental and computational biophysical methods that converge on molecular details including conformer size, intramolecular contacts, and secondary structure propensity.

Impact of immune, inflammatory and nutritional indices on outcome in patients with locally advanced cervical cancer treated with definitive (chemo)radiotherapy.

Objective: Systemic immune, inflammatory, and nutritional indices are prognostic across multiple tumor sites. Comprehensive analysis of these markers in patients with locally advanced cervical cancer (LACC) treated with definitive (chemo)radiotherapy [(C)RT] is limited and may assist with future prognostication.

Methods: For this retrospective cohort study, patients with LACC treated with definitive (C)RT were identified from a comprehensive cancer center's clinicopathological database.

Hyaluronic Acid-Coated Silica Nanoparticles for Targeted Delivery of Nitric Oxide to Cancer Cells.

Drug resistance and off-target toxicity are two of the greatest challenges to chemotherapeutic melanoma treatments. Nitric oxide (NO) represents an attractive alternative to conventional therapeutics due to its numerous anticancer properties and low probability of engendering resistance. As NO is highly reactive, macromolecular NO donors are needed for the controlled and targeted delivery of NO for therapeutic applications.

Transient interdomain interactions modulate the monomeric structural ensemble and self-assembly of Huntingtin Exon 1.

Polyglutamine expansion (≥ 36 residues) within the N-terminal exon-1 of Huntingtin (Httex1) leads to Huntington's disease, a neurodegenerative condition marked by the presence of intranuclear Htt inclusions. Notably, the polyglutamine tract in Httex1 is flanked by an N-terminal coiled-coil domain - N17 (17 amino acids), which undergoes self-association to promote the formation of soluble Httex1 oligomers and brings the aggregation-prone polyQ tracts in close spatial proximity. However, the mechanisms underlying the subsequent conversion of soluble oligomers into insoluble β-rich aggregates with increasing polyQ length, remain unclear.

Uncovering the molecular interactions underlying MBD2 and MBD3 phase separation.

Chromatin organization controls DNA's accessibility to regulatory factors to influence gene expression. Heterochromatin, or transcriptionally silent chromatin enriched in methylated DNA and methylated histone tails, self-assembles through multivalent interactions with its associated proteins into a condensed, but dynamic state. Liquid-liquid phase separation (LLPS) of key heterochromatin regulators, such as heterochromatin protein 1 (HP1), plays an essential role in heterochromatin assembly and function.

Interplay between charge distribution and DNA in shaping HP1 paralog phase separation and localization.

The heterochromatin protein 1 (HP1) family is a crucial component of heterochromatin with diverse functions in gene regulation, cell cycle control, and cell differentiation. In humans, there are three paralogs, HP1α, HP1β, and HP1γ, which exhibit remarkable similarities in their domain architecture and sequence properties. Nevertheless, these paralogs display distinct behaviors in liquid-liquid phase separation (LLPS), a process linked to heterochromatin formation.

Prospective validation of a machine learning model for applicator and hybrid interstitial needle selection in high-dose-rate (HDR) cervical brachytherapy.

Purpose: To Demonstrate the clinical validation of a machine learning (ML) model for applicator and interstitial needle prediction in gynecologic brachytherapy through a prospective clinical study in a single institution.

Methods: The study included cervical cancer patients receiving high-dose-rate brachytherapy using intracavitary (IC) or hybrid interstitial (IC/IS) applicators. For each patient, the primary radiation oncologist contoured the high-risk clinical target volume on a pre-brachytherapy MRI, indicated the approximate applicator location, and made a clinical determination of the first fraction applicator.

A new species of the species group (Squamata, Gekkonidae) from Lao Cai Province, Vietnam.

We describe a new species of the genus based on five adult specimens from Bac Ha District, Lao Cai Province, northern Vietnam. is distinguished from the remaining Indochinese bent-toed geckos by a combination of the following morphological characteristics: medium size (SVL up to 89.5 mm); dorsal tubercles in 17-19 irregular transverse rows; ventral scales in 32-34 longitudinal rows at midbody; precloacal pores present in both sexes, 9 or 10 in males, 8 or 9 in females; 12-15 enlarged femoral scales on each thigh; femoral pores 9-12 in males, 5-10 in females; postcloacal tubercles 2-4; lamellae under toe IV 21-23; dorsal pattern consisting of 5 or 6 irregular dark bands, a thin neckband without V-shape or triangle shape in the middle, top of head with dark brown blotches; subcaudal scales transversely enlarged.

Long-lasting forms of plasticity through patterned ultrasound-induced brainwave entrainment.

Achieving long-lasting neuronal modulation with low-intensity, low-frequency ultrasound is challenging. Here, we devised theta burst ultrasound stimulation (TBUS) with gamma bursts for brain entrainment and modulation of neuronal plasticity in the mouse motor cortex. We demonstrate that two types of TBUS, intermittent and continuous TBUS, induce bidirectional long-term potentiation or depression-like plasticity, respectively, as evidenced by changes in motor-evoked potentials.

Association of green tea consumption with prediabetes, diabetes and markers of glucose metabolism in rural Vietnam: a cross-sectional study.

The literature on green tea consumption and glucose metabolism has reported conflicting findings. This cross-sectional study examined the association of green tea consumption with abnormal glucose metabolism among 3000 rural residents aged 40-60 years in Khánh Hòa province in Vietnam. Multinomial logistic regression analysis was conducted to examine the association of green tea consumption (0, < 200, 200-< 400, 400-< 600 or ≥ 600 ml/d) with prediabetes and diabetes (based on the American Diabetes Association criteria).

BDNF/TrkB Signaling Inhibition Suppresses Astrogliosis and Alleviates Mechanical Allodynia in a Partial Crush Injury Model.

Neuropathic pain presents a formidable clinical challenge due to its persistent nature and limited responsiveness to conventional analgesic treatments. While significant progress has been made in understanding the role of spinal astrocytes in neuropathic pain, their contribution and functional changes following a partial crush injury (PCI) remain unexplored. In this study, we investigated structural and functional changes in spinal astrocytes during chronic neuropathic pain, employing a partial crush injury model.

Ultrasonocoverslip: In-vitro platform for high-throughput assay of cell type-specific neuromodulation with ultra-low-intensity ultrasound stimulation.

Brain stimulation with ultra-low-intensity ultrasound has rarely been investigated due to the lack of a reliable device to measure small neuronal signal changes made by the ultra-low intensity range. We propose Ultrasonocoverslip, an ultrasound-transducer-integrated-glass-coverslip that determines the minimum intensity for brain cell activation. Brain cells can be cultured directly on Ultrasonocoverslip to simultaneously deliver uniform ultrasonic pressure to hundreds of cells with real-time monitoring of cellular responses using fluorescence microscopy and single-cell electrophysiology.

Accelerated Partial Breast Irradiation Using 5 Daily Fractions: A Prospective, Phase 2, Multicenter Trial of Cosmetic Outcomes and Toxicity-ACCEL Final Results.

Purpose: This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI).

Methods And Materials: The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI.

Clinical implementation of 3D transvaginal ultrasound for intraoperative guidance of needle implant in template interstitial gynecologic high-dose-rate brachytherapy.

Purpose: To demonstrate novel clinical implementation of a 3D transvaginal ultrasound (3DTVUS) system for intraoperative needle insertion guidance in perineal template interstitial gynecologic high-dose-rate brachytherapy and assess its impact on implant quality.

Methods And Materials: Interstitial implants began with preimplant 3DTVUS to visualize the tumor and anatomy, with intermittent 3DTVUS to assess the implant and guide needle adjustment. Analysis includes visualization of the implant relative to anatomy, identification of cases where 3DTVUS is beneficial, dosimetry, and a survey distributed to 3DTVUS clinicians.

Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery.

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery.

Interplay between charge distribution and DNA in shaping HP1 paralog phase separation and localization.

The heterochromatin protein 1 (HP1) family is a crucial component of heterochromatin with diverse functions in gene regulation, cell cycle control, and cell differentiation. In humans, there are three paralogs, HP1α, HP1β, and HP1γ, which exhibit remarkable similarities in their domain architecture and sequence properties. Nevertheless, these paralogs display distinct behaviors in liquid-liquid phase separation (LLPS), a process linked to heterochromatin formation.

Challenges in studying the liquid-to-solid phase transitions of proteins using computer simulations.

"Membraneless organelles," also referred to as biomolecular condensates, perform a variety of cellular functions and their dysregulation is implicated in cancer and neurodegeneration. In the last two decades, liquid-liquid phase separation (LLPS) of intrinsically disordered and multidomain proteins has emerged as a plausible mechanism underlying the formation of various biomolecular condensates. Further, the occurrence of liquid-to-solid transitions within liquid-like condensates may give rise to amyloid structures, implying a biophysical link between phase separation and protein aggregation.

8-Methoxypsoralen Induces Apoptosis by Upregulating p53 and Inhibits Metastasis by Downregulating MMP-2 and MMP-9 in Human Gastric Cancer Cells.

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells.

Hidden in the jungle of Vietnam: a new species of (Amphibia, Anura, Dicroglossidae) from Ngoc Linh Mountain.

A new species of is described from Ngoc Linh Mountain of the Kon Tum Massif in central Vietnam. The new species is morphologically distinguishable from its congeners on the basis of a combination of the following diagnostic characters: SVL 79.6-84.

Beneficial and detrimental effects of non-specific binding during DNA hybridization.

DNA strands have to sample numerous states to find the alignment that maximizes Watson-Crick-Franklin base pairing. This process depends strongly on sequence, which affects the stability of the native duplex as well as the prevalence of non-native inter- and intramolecular helices. We present a theory that describes DNA hybridization as a three-stage process: diffusion, registry search, and zipping.

Molecular interactions underlying the phase separation of HP1α: role of phosphorylation, ligand and nucleic acid binding.

Heterochromatin protein 1α (HP1α) is a crucial element of chromatin organization. It has been proposed that HP1α functions through liquid-liquid phase separation (LLPS), which allows it to compact chromatin into transcriptionally repressed heterochromatin regions. In vitro, HP1α can undergo phase separation upon phosphorylation of its N-terminus extension (NTE) and/or through interactions with DNA and chromatin.