This commentary highlights the importance and implications of the study “Quadruple-band synglisis enables high thermoelectric efficiency in earth-abundant tin sulfide crystals”, led by C. Chang and L. Zhao, published in Science. They improved the thermoelectric efficiency by activating quadruple-band synglisis and facilitating carrier transport in tin sulfide crystals, and successfully developed an optical pump–terahertz probe technique in reflection mode to diagnose the carrier dynamics for high-conductivity bulk thermoelectric materials. This study inspires mutual promotion and complementary development between the fields of thermoelectrics and terahertz technology.

Self-propulsion enzymatic nanomotors have shown tremendous potential in the field of diagnostics. In a study led by Wang and coworkers, nanoenzyme-driven cup-shaped nanomotors were designed for enhanced cell penetration and synergistic photodynamic/thermal treatments under single near-infrared laser irradiation. By combining the concepts of self-propulsion enzymatic nanomotors and synergistic dual-modal therapy, this work provides a new idea and tool for the application of nanomotors in the biomedical field.

The Hopf whole-brain model, based on structural connectivity, overcomes limitations of traditional structural or functional connectivity-focused methods by incorporating heterogeneity parameters, quantifying dynamic brain characteristics in healthy and diseased states. Traditional parameter fitting techniques lack precision, restricting broader use. To address this, we validated parameter fitting methods using simulated networks and synthetic models, introducing improvements such as individual-specific initialization and optimized gradient descent, which reduced individual data loss. We also developed an approximate loss function and gradient adjustment mechanism, enhancing parameter fitting accuracy and stability. Applying this refined method to datasets for major depressive disorder (MDD) and autism spectrum disorder (ASD), we identified differences in brain regions between patients and healthy controls, explaining related anomalies. This rigorous validation is crucial for clinical application, paving the way for precise neuropathological identification and novel treatments in neuropsychiatric research, demonstrating substantial potential in clinical neurology.

Epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signaling is highly activated in various types of cancer. The long noncoding RNAs induced by this pathway and their roles in colorectal cancer (CRC) have not been fully elucidated. In this study, based on the profiling of long noncoding RNAs triggered by EGFR/MAPK signaling, we identified that ESSENCE (EGF [epidermal growth factor] Signal Sensing CAD’s Effect; ENST00000415336), which is mediated by the transcription factor early growth response factor 1, functions as a potent oncogenic molecule that predicts poor prognosis in CRC. Mechanistically, ESSENCE directly interacts with carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) and competitively attenuates CAD degradation mediated by its newly discovered E3 ligase KEAP1, thereby suppressing ferroptosis and promoting CRC progression. Importantly, combinational treatment of the mitogen-activated extracellular signal-regulated kinase inhibitor selumetinib and ferroptosis inducer sulfasalazine synergistically suppresses ESSENCE-high CRC in a patient-derived xenograft mouse model. Taken together, these findings demonstrate the crucial role of ESSENCE in mediating CRC progression by regulating CAD stabilization and suggest a therapeutic strategy of targeting the ESSENCE–CAD axis in CRC.

Graded hypoxia is a common microenvironment in malignant solid tumors. As a central regulator in the hypoxic response, hypoxia-inducible factor-1 (HIF-1) can induce multiple cellular processes including glycolysis, angiogenesis, and necroptosis. How cells exploit the HIF-1 pathway to coordinate different processes to survive hypoxia remains unclear. We developed an integrated model of the HIF-1α network to elucidate the mechanism of cellular adaptation to hypoxia. By numerical simulations and bifurcation analysis, we found that HIF-1α is progressively activated with worsening hypoxia due to the sequential deactivation of the hydroxylases prolyl hydroxylase domain enzymes and factor inhibiting HIF (FIH). Bistable switches control the activation and deactivation processes. As a result, glycolysis, immunosuppression, angiogenesis, and necroptosis are orderly elicited in aggravating hypoxia. To avoid the excessive accumulation of lactic acid during glycolysis, HIF-1α induces monocarboxylate transporter and carbonic anhydrase 9 sequentially to export intracellular hydrogen ions, facilitating tumor cell survival. HIF-1α-induced miR-182 facilitates vascular endothelial growth factor production to promote angiogenesis under moderate hypoxia. The imbalance between accumulation and removal of lactic acid in severe hypoxia may result in acidosis and induce cell necroptosis. In addition, the deactivation of FIH results in the destabilization of HIF-1α in anoxia. Collectively, HIF-1α orchestrates the adaptation of tumor cells to hypoxia by selectively inducing its targets according to the severity of hypoxia. Our work may provide clues for tumor therapy by targeting the HIF-1 pathway.

Endometriosis is marked by the ectopic growth, spread, and invasion of endometrial tissue beyond the uterus, resulting in recurrent bleeding, pain, reproductive challenges, and the formation of nodules or masses. Despite advancements in detection methods like ultrasound and laparoscopy, these techniques remain limited by low specificity and invasiveness, underscoring the need for a highly specific, noninvasive in vitro diagnostic method. This study investigates the potential of using menstrual blood as a noninvasive diagnostic sample for endometriosis by targeting genetic and inflammatory markers associated with endometriosis lesions. A novel digital droplet enzyme-linked immunosorbent assay (ddELISA) was developed, leveraging SiO₂ nanoparticles for the femtomolar-sensitive detection of inflammatory cytokines (OPN, IL-10, IL-6) in menstrual blood. Single-cell RNA sequencing revealed differentiation patterns across endometrial tissues and menstrual blood, affirming that menstrual blood replicates key inflammatory and immune properties of endometriosis. Furthermore, endometriosis menstrual blood endometrial cells derived from human menstrual blood displayed similar properties to endometrial stromal cells in endometriosis lesions, validating menstrual blood as a suitable in vitro diagnostic sample. In contrast to traditional ELISA, ddELISA supports multi-target detection with enhanced sensitivity and reduced processing time, allowing precise biomarker analysis from minimal sample volumes. Our ddELISA-based approach shows promise as a rapid, accessible, and accurate diagnostic tool for endometriosis, with potential for practical clinical application.

A new photoelectrocatalytic water purification system was investigated by combining photocatalysis and electrochemistry. This configuration achieves simultaneous removal of both organic compounds and inorganic heavy metal ions from water by taking a carbon electrode as the working electrode and another electrode coated with a photocatalyst as the counter electrode. A negative bias potential is imparted onto the working electrode to induce the reduction of heavy metal ions, whereas the photocatalytic degradation of organic pollutants on the counter electrode is amplified via the transfer of photoexcited electrons from the counter electrode to the working electrode. Evaluations conducted in bulk solutions demonstrated that photoelectrocatalysis surpassed photocatalysis by yielding an organic matter degradation efficiency 2.3 times higher, successfully degrading 98% of a 10 μM methylene blue solution within 2 h. Simultaneously, the system realized the recovery of heavy metal ions, including copper, lead, and cadmium. This new photoelectrocatalytic water purification system was further integrated with microchannels, and the testing data affirm the substantial potential for system miniaturization.

Background: A century ago, a mystery between a virus and Parkinson’s disease (PD) was described. Owing to the limitation of human brain biopsy and the challenge of electron microscopy in observing virions in human brain tissue, it has been difficult to study the viral etiology of PD. Recent discovery of virobiota reveals that viruses coexist with humans as symbionts. Newly developed transcriptomic sequencing and novel bioinformatic approaches for mining the encrypted virome in human transcriptome make it possible to study the relationship between symbiotic viruses and PD. Nevertheless, whether viruses exist in the human substantia nigra (SN) and whether symbiotic viruses underlie PD pathogenesis remain unknown. Methods: We collected current worldwide human SN transcriptomic datasets from the United States, the United Kingdom, the Netherlands, and Switzerland. We used bioinformatic approaches including viruSITE and the Viral-Track to identify the existence of viruses in the SN of patients. The comprehensive RNA sequencing-based virome analysis pipeline was used to characterize the virobiota in the SN. The Pearson’s correlation analysis was used to examine the association between the viral RNA fragment counts (VRFCs) and PD-related human gene sequencing reads in the SN. The differentially expressed genes (DEGs) in the SN between PD patients and non-PD individuals were used to examine the molecular signatures of PD and also evaluate the impact of symbiotic viruses on the SN. Findings: We observed the existence of viruses in the human SN. A dysbiosis of virobiota was found in the SN of PD patients. A marked correlation between VRFC and PD-related human gene expression was detected in the SN of PD patients. These PD-related human genes correlated to VRFC were named as the virus-correlated PD-related genes (VPGs). We identified 3 bacteriophages (phages), including the Proteus phage VB_PmiS-Isfahan, the Escherichia phage phiX174, and the Lactobacillus phage Sha1, that might impair the gene expression of neural cells in the SN of PD patients. The Proteus phage VB_PmiS-Isfahan was a common virus in the SN of patients from the United Kingdom, the Netherlands, and Switzerland. VPGs and DEGs together highlighted that the phages might dampen dopamine biosynthesis and weaken the cGAS-STING function. Interpretation: This is the first study to discover the involvement of phages in PD pathogenesis. A lifelong low symbiotic viral load in the SN may be a contributor to PD pathogenesis. Our findings unlocked the black box between brain virobiota and PD, providing a novel insight into PD etiology from the perspective of phage–human symbiosis.

Previous studies have indicated that major depressive disorder (MDD) patients with suicidal ideation (SI) present abnormal functional connectivity (FC) and network organization in node-centric brain networks, ignoring the interactions among FCs. Whether the abnormalities of edge interactions affect the emergence of SI and are related to the gene expression remains largely unknown. In this study, resting-state functional magnetic resonance imaging (fMRI) data were collected from 90 first-episode, drug-naive MDD with suicidal ideation (MDDSI) patients, 60 first-episode, drug-naive MDD without suicidal ideation (MDDNSI) patients, and 98 healthy controls (HCs). We applied the methodology of edge-centric network analysis to construct the functional brain networks and calculate the nodal entropy. Furthermore, we examined the relationships between nodal entropy alterations and gene expression. The MDDSI group exhibited significantly lower subnetwork entropy in the dorsal attention network (DAN) and significantly greater subnetwork entropy in the default mode network than the MDDNSI group. The visual learning score of the measurement and treatment research to improve cognition in schizophrenia (MATRICS) consensus cognitive battery was negatively correlated with the subnetwork entropy of DAN in the MDDSI group. The support vector machine model based on nodal entropy achieved an accuracy of 81.87% when distinguishing the MDDNSI and MDDSI. Additionally, the changes in SI-related nodal entropy were associated with the expression of genes in cell signaling and interactions, as well as immune and inflammatory responses. These findings reveal the abnormalities in nodal entropy between the MDDSI and MDDNSI groups, demonstrated their association with molecular functions, and provided novel insights into the neurobiological underpinnings and potential markers for the prediction and prevention of suicide.

Stress-induced apoptosis presents an obstacle to bone marrow mesenchymal stem cell (BMSC) transplantation to repair steroid-induced osteonecrosis of the femoral head (SONFH). Thus, appropriate intervention strategies should be explored to mitigate this. In our previous study, we discovered a new subgroup of BMSCs—the oxidative stress-resistant BMSCs (OSR-BMSCs)—which can survive the oxidative stress microenvironment in the osteonecrotic area, through a mechanism that currently remains unclear. In this study, we found that B-lymphoid tyrosine kinase (BLK) may be the crucial factor regulating the oxidative stress resistance of OSR-BMSCs, as it is highly expressed in these cells. Knockdown of BLK eliminated oxidative stress resistance, aggravated oxidative stress-induced apoptosis, reduced the survival of OSR-BMSCs in the oxidative stress microenvironment of the osteonecrotic area, and greatly weakened the transplantation efficacy of OSR-BMSCs for SONFH. By contrast, BLK was weakly expressed in oxidative stress-sensitive BMSCs (OSS-BMSCs). Overexpression of BLK in susceptible OSS-BMSCs allowed them to acquire oxidative stress resistance, inhibited oxidative stress-induced apoptosis, promoted their survival in the osteonecrotic area, and improved the transplantation efficacy of OSS-BMSCs for SONFH. Mechanistically, BLK concurrently activates redox and apoptotic signaling networks through its tyrosine kinase activity, which confers oxidative stress resistance to BMSCs and inhibits their stress-induced apoptosis of BMSCs. Herein, we report that OSR-BMSCs have intrinsic oxidative stress resistance that is conferred and mediated by BLK. This finding provides a potential new intervention strategy for improving the survival of transplanted BMSCs and the therapeutic efficacy of BMSC transplantation for SONFH.