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Ultrasound (US) imaging is a widely used diagnostic method in clinics. Real-time-generated US images are used for rapid diagnosis without harm to patients. The quality of US imaging highly depends on the skill of the physician due to the differences among physicians. Techniques for autonomous robotic ultrasound (AU-RUS) acquisitions are expected to become an effective means to improve the level of US diagnosis, reduce the workload of physicians, and improve the standardization of US imaging quality. This paper aims to summarize the current research status of techniques for AU-RUS acquisitions, and to discuss the research trends and challenges regarding related technologies. Firstly, the techniques for AU-RUS acquisitions and systems are outlined. The techniques for teleoperated or autonomous US acquisitions are briefly discussed. Representative RUS acquisition systems are introduced. Then, the current research status of AU-RUS acquisitions is reviewed from four research directions: force sensitivity and control, scanning path-planning and positioning, US treatment guidance, and US image processing technology and quality assessment optimization. This review provides a decision-oriented autonomy perspective by mapping typical methods to workflow components across the stages of perception, decision-making, and execution. We identify major deployment bottlenecks, including safety-verifiable autonomy and failure recovery, motion compensation under deformation, and the lack of standardized, clinically meaningful US image quality metrics. Finally, the shortcomings of current research are summarized and analyzed, and the research trends and challenges for AU-RUS acquisitions are prospected.

Background Considering melanoma is the deadliest malignancy among dermatoma and presently lacks effective therapies, there is an urgent need to investigate the potential mechanisms underlying melanoma metastasis and determine prospective therapeutic targets for precise treatment of melanoma. Method Hub genes in melanoma metastasis were identified by analyzing RNA‐seq data (mRNA, miRNA, and lncRNA) obtained from TCGA database. Then the identified hub genes were validated in human tissues with qRT‐PCR, followed by survival analysis. Competing endogenous RNAs of the hub genes were defined to clarify potential molecular mechanism of melanoma progression. Then central gene‐related signaling pathways were analyzed, followed by immune cell abundance analysis in tumor microenvironment with CYTERSORTx. Result A tetrad of IL2RA, IL2RG, IFNG, and IL7R genes were determined as hub genes and verified by qRT‐PCR, which were significantly associated with unfavorable prognosis in melanoma. LINC02446, LINC01857, and LINC02384 may act as competing endogenous lncRNAs of IL2RA and IL7R through absorbing their shared miR.891a.5p and miR.203b.3p. JAK—STAT signaling pathway identified as the most relevant pathway in melanoma metastasis, as well as a wealthy of genes including TNFRSF 13B, TNFRSF17, TNFRSF9, TNFRSF8, TNFRSF13C, TNFRSF11B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7, may induce tumor autoimmune suppression through enhancing regulatory T‐cell abundance and performance in the tumor microenvironment. And regulatory T‐cell proportion was indeed critically elevated in metastatic melanoma relative to primary melanoma, as well as in highly expressed IL2RA, IL2RG, IL7R, and IFNG group than their respective counterparts. Conclusion Elevated IL2RA, IL2RG, IL7R, and IFNG expression may play a central role in promoting melanoma metastasis through up regulation of intratumoral regulatory T—cell proportion mainly by activation of JAK—STAT signaling pathway. LINC02446, LINC01857, and LINC02384 may stimulate melanoma progression by reducing tumor‐protecting miR.891a.5p and miR.203b.3p. A number of identified molecules including TNFRSF13B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7 can serve as future therapeutic targets in melanoma treatment. Elevated IL2RA, IL2RG, IL7R, and IFNG expression may play a central role in promoting melanoma metastasis via increase in intratumoral regulatory T cell proportion, mainly by activation of the JAK–STAT signaling pathway. LINC02446, LINC01857, and LINC02384 may stimulate melanoma progression by reducing tumor‐protecting miR.891a.5p and miR.203b.3p. A number of identified molecules, including TNFRSF13B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7, can serve as future therapeutic targets in the treatment of melanoma.

POLE/POLD1 gene variants have been suggested as potential markers for immunotherapy due to their significant association with the tumor mutational burden (TMB), an effective indicator for response prediction in immunotherapy. However, the correlation of POLE/POLD1 variants with MSI, MMR, TMB, MMR-related and key driver gene mutations needs to be defined to support patient recruitment and therapeutic effect assessment in immunotherapy. 1,392 Chinese cancer patients were recruited, and the correlation of POLE/POLD1 variants with existing immunotherapeutic markers and cancer pathways was investigated. A next-generation sequencing panel including 605 cancer-related genes was used for variant sequencing. It was found that the frequency of POLE variants was not statistically different from that in COSMIC database, while the frequency of POLD1 variants was significantly higher in lung cancer. c.857 C > G and c.2091dupC were potential high frequency variants in Chinese cancer patients. Patients carrying POLE damaging variants were significantly younger than POLE/POLD1 WT patients. Patients carrying POLE/POLD1 damaging variants exhibited significantly higher TMB and frequency of MMR gene variants than POLE/POLD1 WT patients. Patients with POLE damaging variants also exhibited significantly higher frequency of driver gene variants than POLE/POLD1 WT patients. Further analysis showed that POLE damaging variants may affect the cancer development through MMR, TGFβ and RTK/RAS/RAF signaling pathways, and POLD1 through MMR pathways. In conclusion, this study identified key characteristics and regions of POLE/POLD1 genes that correlates with TMB, MMR gene mutations and key driver gene mutations, and provided theoretical and practical basis for patient selection based on POLE/POLD1 gene status in immunotherapy.

Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7 , which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn 2+ in modulating B cell receptor signal strength and positive selection. Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn 2+ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.

Evaluating the therapeutic response and survival of lung cancer patients receiving first‐line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long‐term survival of lung cancer patients receiving first‐line chemotherapy are discovered. Whole‐exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non‐small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1–C4). The long‐term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed (P < 0.001). NSCLC patients can be divided into three subtypes (S1–S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first‐line chemotherapy in lung cancer. Evaluating the therapeutic response and survival of lung cancer patients receiving first‐line chemotherapy has always been difficult. In this study whole‐exome sequencing is performed on pretherapeutic tissue samples of 186 patients (145 non‐small cell lung cancer and 41 small cell lung cancer). Several molecular signatures associated with response and survival to first‐line chemotherapy in lung cancer are identified.

Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn in modulating B cell receptor signal strength and positive selection.